Pub Date : 2008-01-01DOI: 10.1101/087969752.50.439
K. Luo
The TGF-β family of cytokines regulates a wide array of biological activities in various cell types and at different developmental stages. Smad proteins are critical mediators of TGF-β, BMP (bone morphogenetic protein), and activin signaling (Itoh et al. 2000; Moustakas et al. 2001; Derynck and Zhang 2003; Shi and Massague 2003). Upon phosphorylation by the active type I receptor kinase, R-Smads (receptor-activated Smads) form a heteromeric complex with the co-Smads (common-mediator Smads) and translocate into the nucleus, where they interact with sequence-specific DNA-binding cofactors and transcriptional coactivators or corepressors to regulate the expression of target genes (see Chapter 9). This pathway is integrated into the overall signaling network in the cell through cross-talk with other signaling pathways at multiple levels, which depend on the specific physiological context. These cross-talk activities play important roles in the regulation of various biological responses induced by TGF-β, BMP, or activin. In this chapter, the cross-talk of Smads with Wnt signaling, Notch signaling, MAP kinase signaling, phosphatidylinositol-3 (PI3) kinase-Akt, protein kinase C (PKC), and Jak-Stat pathway will be discussed. CROSS-TALK WITH WNT SIGNALING PATHWAY Combinatorial signaling often occurs in early embryos to allow overlapping signaling pathways to specify different territories and cell fates. The Wnt, BMP and TGF-β, and the Notch signaling pathways are integrated in this combinatorial signaling and often function in a synergistic or antagonistic manner to regulate vertebrate development. The Wnt signaling pathway has an important role in cell fate determination, self-renewal and maintenance of stem cell and early progenitor cells at...
TGF-β细胞因子家族调节各种细胞类型和不同发育阶段的广泛生物活性。Smad蛋白是TGF-β、BMP(骨形态发生蛋白)和激活素信号传导的关键介质(Itoh等，2000;Moustakas et al. 2001;Derynck and Zhang 2003;Shi和Massague 2003)。在被活性I型受体激酶磷酸化后，R-Smads(受体激活的Smads)与co-Smads(共同介质Smads)形成异质复合物并转运到细胞核中。它们与序列特异性的dna结合辅助因子和转录共激活因子或共抑制因子相互作用，以调节靶基因的表达(见第9章)。该途径通过与其他信号通路在多个水平上的串扰，整合到细胞中的整个信号网络中，这取决于特定的生理环境。这些串扰活性在调节TGF-β、BMP或激活素诱导的各种生物反应中发挥重要作用。在本章中，我们将讨论Smads与Wnt信号、Notch信号、MAP激酶信号、磷脂酰肌醇-3 (PI3)激酶- akt、蛋白激酶C (PKC)和Jak-Stat通路的相互作用。与WNT信号通路的串扰组合信号通路经常发生在早期胚胎，允许重叠的信号通路指定不同的区域和细胞命运。Wnt、BMP、TGF-β和Notch信号通路整合在这种组合信号通路中，通常以协同或拮抗的方式调节脊椎动物的发育。Wnt信号通路在干细胞和早期祖细胞的细胞命运决定、自我更新和维持中具有重要作用。
{"title":"15 Regulation of the Smad Pathway by Signaling Cross-Talk","authors":"K. Luo","doi":"10.1101/087969752.50.439","DOIUrl":"https://doi.org/10.1101/087969752.50.439","url":null,"abstract":"The TGF-β family of cytokines regulates a wide array of biological activities in various cell types and at different developmental stages. Smad proteins are critical mediators of TGF-β, BMP (bone morphogenetic protein), and activin signaling (Itoh et al. 2000; Moustakas et al. 2001; Derynck and Zhang 2003; Shi and Massague 2003). Upon phosphorylation by the active type I receptor kinase, R-Smads (receptor-activated Smads) form a heteromeric complex with the co-Smads (common-mediator Smads) and translocate into the nucleus, where they interact with sequence-specific DNA-binding cofactors and transcriptional coactivators or corepressors to regulate the expression of target genes (see Chapter 9). This pathway is integrated into the overall signaling network in the cell through cross-talk with other signaling pathways at multiple levels, which depend on the specific physiological context. These cross-talk activities play important roles in the regulation of various biological responses induced by TGF-β, BMP, or activin. In this chapter, the cross-talk of Smads with Wnt signaling, Notch signaling, MAP kinase signaling, phosphatidylinositol-3 (PI3) kinase-Akt, protein kinase C (PKC), and Jak-Stat pathway will be discussed. CROSS-TALK WITH WNT SIGNALING PATHWAY Combinatorial signaling often occurs in early embryos to allow overlapping signaling pathways to specify different territories and cell fates. The Wnt, BMP and TGF-β, and the Notch signaling pathways are integrated in this combinatorial signaling and often function in a synergistic or antagonistic manner to regulate vertebrate development. The Wnt signaling pathway has an important role in cell fate determination, self-renewal and maintenance of stem cell and early progenitor cells at...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"40 1","pages":"439-459"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86274079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Activins and the structurally and functionally related inhibins belong to the transforming growth factor-β (TGF-β) family of growth factors. Activins and inhibins have central roles in regulating follicle-stimulating hormone (FSH) release and in coordinating reproductive physiology. Inhibins function as classical endocrine hormones, whereas both activins and inhibins have localized autocrine and paracrine roles. Activins have additional functions outside of the reproductive systems as regulators of cell growth and differentiation, particularly in response to injury and inflammation. This chapter discusses the mechanisms involved in activin and inhibin activities and the roles of these factors in reproductive and other tissues. STRUCTURES AND SYNTHESIS OF ACTIVINS AND INHIBINS A hormone termed “inhibin” was proposed to exist in 1932 (McCullagh 1932). Inhibin was defined as a nonsteroidal, water-soluble factor in gonadal extracts that prevents stereotypical changes in the morphology of the pituitary that appeared after castration. After the identification of the pituitary cell types and their corresponding hormones, this definition was refined: Inhibin exerts a direct effect on pituitary gonadotrope cells, leading to a specific suppression of FSH release, without altering the release of luteinizing hormone (LH) (de Kretser et al. 1988; Vale et al. 1988). Biochemical purification of inhibin was undertaken using this activity on pituitary cells as an assay. Secretions of various gonadal fluids were found to be rich sources of inhibin and were thus used as source material for purification. Inhibins—and in the process, activins—were eventually purified to apparent homogeneity from these sources based on their effects on FSH...
激活素与结构和功能相关的抑制素属于转化生长因子-β (TGF-β)生长因子家族。激活素和抑制素在调节卵泡刺激素(FSH)释放和协调生殖生理方面起着中心作用。抑制素是典型的内分泌激素，而激活素和抑制素都具有局部的自分泌和旁分泌作用。激活素在生殖系统之外还有其他功能，如调节细胞生长和分化，特别是在对损伤和炎症的反应中。本章讨论了激活素和抑制素活性的机制，以及这些因子在生殖和其他组织中的作用。激活素和抑制素的结构和合成一种被称为“抑制素”的激素在1932年被提出(McCullagh 1932)。抑制素被定义为性腺提取物中的一种非甾体水溶性因子，可防止去势后出现的垂体形态的典型变化。在确定了垂体细胞类型及其相应的激素后，对这一定义进行了细化:抑制素直接作用于垂体促性腺激素细胞，导致特异性抑制FSH的释放，而不改变促黄体生成素(LH)的释放(de Kretser et al. 1988;Vale et al. 1988)。利用抑制素在垂体细胞上的活性进行生化纯化。各种性腺液体的分泌物被发现是抑制素的丰富来源，因此被用作纯化的源材料。基于抑制素对卵泡刺激素的影响，抑制素和在这个过程中，激活素最终从这些来源中纯化出来，达到明显的同质性……
{"title":"4 Activins and Inhibins","authors":"E. Wiater, W. Vale","doi":"10.1101/087969752.50.79","DOIUrl":"https://doi.org/10.1101/087969752.50.79","url":null,"abstract":"Activins and the structurally and functionally related inhibins belong to the transforming growth factor-β (TGF-β) family of growth factors. Activins and inhibins have central roles in regulating follicle-stimulating hormone (FSH) release and in coordinating reproductive physiology. Inhibins function as classical endocrine hormones, whereas both activins and inhibins have localized autocrine and paracrine roles. Activins have additional functions outside of the reproductive systems as regulators of cell growth and differentiation, particularly in response to injury and inflammation. This chapter discusses the mechanisms involved in activin and inhibin activities and the roles of these factors in reproductive and other tissues. STRUCTURES AND SYNTHESIS OF ACTIVINS AND INHIBINS A hormone termed “inhibin” was proposed to exist in 1932 (McCullagh 1932). Inhibin was defined as a nonsteroidal, water-soluble factor in gonadal extracts that prevents stereotypical changes in the morphology of the pituitary that appeared after castration. After the identification of the pituitary cell types and their corresponding hormones, this definition was refined: Inhibin exerts a direct effect on pituitary gonadotrope cells, leading to a specific suppression of FSH release, without altering the release of luteinizing hormone (LH) (de Kretser et al. 1988; Vale et al. 1988). Biochemical purification of inhibin was undertaken using this activity on pituitary cells as an assay. Secretions of various gonadal fluids were found to be rich sources of inhibin and were thus used as source material for purification. Inhibins—and in the process, activins—were eventually purified to apparent homogeneity from these sources based on their effects on FSH...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"39 1","pages":"79-120"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89707396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-01-01DOI: 10.1101/087969784.52.463
J. Aimone, Laurenz Wiskott
One of the most intriguing differences between adult and developmental neurogenesis is that in the adult brain, new neurons are integrating into already-developed, functioning circuits. Newborn neurons develop highly complex neuronal morphology—an impressive feat, considering that the extracellular signaling environment (thought to be important during development) is considerably different in the adult. Adult neurogenesis has been observed in most animal species, both in the normal course of life and in response to injury in many nonmammals. The fact that adult neurogenesis is essentially limited to two regions in mammalian brains suggests that the addition of new neurons to these regions (the olfactory bulb [OB] and dentate gyrus [DG]) is of particular importance. Although the function of regenerative neurogenesis is self-evident, the purpose for lifelong neurogenesis remains unclear. There are several reasons why taking a computational modeling approach has potential. One is that any effect of adding new neurons will first be manifested computationally in the network and will only then be observed behaviorally. Modeling can permit the observation of an effect that otherwise would go unseen in standard behavioral assays. This provides a framework by which new predictions can be made that can be specifically tested experimentally. Furthermore, a well-developed computational model or theory can be altered in a manner that is impractical or impossible in animal models, such as increasing the rate of neurogenesis by tenfold or studying the effects of neurogenesis in nonneurogenic areas. Finally, modeling the computational aspects of a system often helps focus future experiments,..
{"title":"22 Computational Modeling of Adult Neurogenesis","authors":"J. Aimone, Laurenz Wiskott","doi":"10.1101/087969784.52.463","DOIUrl":"https://doi.org/10.1101/087969784.52.463","url":null,"abstract":"One of the most intriguing differences between adult and developmental neurogenesis is that in the adult brain, new neurons are integrating into already-developed, functioning circuits. Newborn neurons develop highly complex neuronal morphology—an impressive feat, considering that the extracellular signaling environment (thought to be important during development) is considerably different in the adult. Adult neurogenesis has been observed in most animal species, both in the normal course of life and in response to injury in many nonmammals. The fact that adult neurogenesis is essentially limited to two regions in mammalian brains suggests that the addition of new neurons to these regions (the olfactory bulb [OB] and dentate gyrus [DG]) is of particular importance. Although the function of regenerative neurogenesis is self-evident, the purpose for lifelong neurogenesis remains unclear. There are several reasons why taking a computational modeling approach has potential. One is that any effect of adding new neurons will first be manifested computationally in the network and will only then be observed behaviorally. Modeling can permit the observation of an effect that otherwise would go unseen in standard behavioral assays. This provides a framework by which new predictions can be made that can be specifically tested experimentally. Furthermore, a well-developed computational model or theory can be altered in a manner that is impractical or impossible in animal models, such as increasing the rate of neurogenesis by tenfold or studying the effects of neurogenesis in nonneurogenic areas. Finally, modeling the computational aspects of a system often helps focus future experiments,..","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"49 1","pages":"463-481"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79895270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It has been close to 30 years since the discovery of transforming growth factors as secreted proteins with the ability to induce a reversible transformed phenotype under some cell culture conditions. Not surprisingly, these findings were very skeptically received, because around that time, oncogenes were being discovered as genes encoding cell-autonomous proteins that genetically endowed the cells to behave and function as cancer cells. The discovery of transforming growth factors led to the concept of autocrine control of cell transformation and, later, of cell differentiation and function. Following its discovery, transforming growth factor-β (TGF-β) was shown to have key functions in a variety of cell and tissue contexts, most notably in cell proliferation and differentiation, development, malignant transformation, and cancer progression. In fact, TGF-β was rediscovered several times as secreted proteins with diverse activities, for example, cartilage-inducing factor, glioblastoma-derived T-cell suppressor factor (GTsF), and growth inhibitor from BSC-1 cells. Following the elucidation of the polypeptide sequence of TGF-β1, it became rapidly apparent through cDNA cloning that there is a family of structurally related proteins that together form the TGF-β family that functions in all metazoans from Planaria and nematodes to Drosophila and vertebrates. Activins and inhibins were discovered as hormones that act on pituitary gonadotrope cells and regulate the release of follicle-stimulating hormone. Research on bone morphogenetic proteins (BMPs) was launched by the observation that the demineralized bone matrix contains bioactive proteins capable of inducing bone and cartilage formation in muscular tissues. Purification of these proteins and subsequent cDNA cloning
{"title":"Preface/Front Matter","authors":"R. Derynck, K. Miyazono","doi":"10.1101/087969752.50.I","DOIUrl":"https://doi.org/10.1101/087969752.50.I","url":null,"abstract":"It has been close to 30 years since the discovery of transforming growth factors as secreted proteins with the ability to induce a reversible transformed phenotype under some cell culture conditions. Not surprisingly, these findings were very skeptically received, because around that time, oncogenes were being discovered as genes encoding cell-autonomous proteins that genetically endowed the cells to behave and function as cancer cells. The discovery of transforming growth factors led to the concept of autocrine control of cell transformation and, later, of cell differentiation and function. Following its discovery, transforming growth factor-β (TGF-β) was shown to have key functions in a variety of cell and tissue contexts, most notably in cell proliferation and differentiation, development, malignant transformation, and cancer progression. In fact, TGF-β was rediscovered several times as secreted proteins with diverse activities, for example, cartilage-inducing factor, glioblastoma-derived T-cell suppressor factor (GTsF), and growth inhibitor from BSC-1 cells. Following the elucidation of the polypeptide sequence of TGF-β1, it became rapidly apparent through cDNA cloning that there is a family of structurally related proteins that together form the TGF-β family that functions in all metazoans from Planaria and nematodes to Drosophila and vertebrates. Activins and inhibins were discovered as hormones that act on pituitary gonadotrope cells and regulate the release of follicle-stimulating hormone. Research on bone morphogenetic proteins (BMPs) was launched by the observation that the demineralized bone matrix contains bioactive proteins capable of inducing bone and cartilage formation in muscular tissues. Purification of these proteins and subsequent cDNA cloning","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81212039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-01-01DOI: 10.1101/087969752.50.989
E. Böttinger
Fibrosis is a cardinal feature of most chronic degenerative diseases and may affect virtually every tissue and organ system. The fibrotic response has been characterized as inappropriate repair by connective tissue resulting in scarring, associated with loss of normal tissue architecture and function. The degeneration of functional cell types and accumulation of mesenchymal cells and extracellular matrix (ECM) typically progress slowly over several years, resulting eventually in organ failure. Fibrotic conditions, irrespective of their diverse etiology, anatomic location, and natural history, share common pathogenetic features: excessive secretion and activation of profibrotic cytokines, influx of inflammatory cells, loss of differentiated epithelial cells, expansion and activation of fibroblastoid cells, and ECM synthesis and organization (Border and Noble 1994; Friedman 2003). Because these features are also observed in normal wound healing, it has been proposed that fibrosis can be conceptualized as “healing without end” or “the dark side of tissue repair” (Border and Noble 1994). Disease-oriented studies in experimental models and human disease universally demonstrate alterations of transforming growth factor-β (TGF-β) expression in tissues affected by fibrosis, including pulmonary fibrosis (Hoyt and Lazo 1989; Raghu et al. 1989), hepatic fibrosis (Czaja et al. 1989; Nakatsukasa et al. 1990), renal fibrosis (Border et al. 1990a; Okuda et al. 1990; Coimbra et al. 1991; Jones et al. 1991), ocular fibrosis (Connor et al. 1989), cardiac fibrosis (Chua et al. 1991), radiation fibrosis (Anscher et al. 1990), and systemic sclerosis and fibrotic skin diseases (Peltonen et al. 1990; Falanga and Julien 1990). TGF-β is the prototypical...
纤维化是大多数慢性退行性疾病的主要特征，几乎可以影响每一个组织和器官系统。纤维化反应的特征是结缔组织不适当的修复导致瘢痕形成，并伴有正常组织结构和功能的丧失。功能性细胞类型的退化和间充质细胞和细胞外基质(ECM)的积累通常在数年内缓慢进展，最终导致器官衰竭。无论其不同的病因、解剖位置和自然历史如何，纤维化疾病都具有共同的发病特征:促纤维化细胞因子的过度分泌和激活、炎症细胞的涌入、分化上皮细胞的丧失、成纤维细胞样细胞的扩张和激活以及ECM的合成和组织(Border和Noble 1994;弗里德曼2003年)。由于这些特征在正常的伤口愈合中也可以观察到，因此有人提出，纤维化可以被概念化为“无终点的愈合”或“组织修复的阴暗面”(Border and Noble 1994)。以疾病为导向的实验模型和人类疾病研究普遍表明，转化生长因子-β (TGF-β)在受纤维化影响的组织中表达改变，包括肺纤维化(Hoyt和Lazo 1989;Raghu et al. 1989)，肝纤维化(Czaja et al. 1989;Nakatsukasa et al. 1990)，肾纤维化(Border et al. 1990;Okuda等人，1990;Coimbra et al. 1991;Jones et al. 1991)、眼纤维化(Connor et al. 1989)、心脏纤维化(Chua et al. 1991)、辐射纤维化(Anscher et al. 1990)、系统性硬化症和纤维化性皮肤病(Peltonen et al. 1990;Falanga and Julien 1990)。TGF-β是典型的…
{"title":"31 TGF-β and Fibrosis","authors":"E. Böttinger","doi":"10.1101/087969752.50.989","DOIUrl":"https://doi.org/10.1101/087969752.50.989","url":null,"abstract":"Fibrosis is a cardinal feature of most chronic degenerative diseases and may affect virtually every tissue and organ system. The fibrotic response has been characterized as inappropriate repair by connective tissue resulting in scarring, associated with loss of normal tissue architecture and function. The degeneration of functional cell types and accumulation of mesenchymal cells and extracellular matrix (ECM) typically progress slowly over several years, resulting eventually in organ failure. Fibrotic conditions, irrespective of their diverse etiology, anatomic location, and natural history, share common pathogenetic features: excessive secretion and activation of profibrotic cytokines, influx of inflammatory cells, loss of differentiated epithelial cells, expansion and activation of fibroblastoid cells, and ECM synthesis and organization (Border and Noble 1994; Friedman 2003). Because these features are also observed in normal wound healing, it has been proposed that fibrosis can be conceptualized as “healing without end” or “the dark side of tissue repair” (Border and Noble 1994). Disease-oriented studies in experimental models and human disease universally demonstrate alterations of transforming growth factor-β (TGF-β) expression in tissues affected by fibrosis, including pulmonary fibrosis (Hoyt and Lazo 1989; Raghu et al. 1989), hepatic fibrosis (Czaja et al. 1989; Nakatsukasa et al. 1990), renal fibrosis (Border et al. 1990a; Okuda et al. 1990; Coimbra et al. 1991; Jones et al. 1991), ocular fibrosis (Connor et al. 1989), cardiac fibrosis (Chua et al. 1991), radiation fibrosis (Anscher et al. 1990), and systemic sclerosis and fibrotic skin diseases (Peltonen et al. 1990; Falanga and Julien 1990). TGF-β is the prototypical...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"03 1","pages":"989-1022"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86272811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-01-01DOI: 10.1101/087969784.52.645
I. Amrein, H. Lipp, R. Boonstra, J. Wojtowicz
This chapter is based on the premise that if we are to acquire a deep understanding of adult neurogenesis—what it is selected for (i.e., its functional and adaptive significance), what causes it to go up or down (e.g., species constraints, reproductive hormones, seasonality, stress, and environmental conditions), and why it declines with age—the research must ultimately be grounded on an evolutionary and ecological foundation. The aphorism of Dobzansky (1973) is particularly apropos: “Nothing in biology makes sense, except in the light of evolution.” Thus, simply focusing on humans and those laboratory species we select for will not be sufficient to crack this enigma. Such a deep understanding may also aid in ameliorating debilitating aspects of the human condition after injury or in disease. This chapter advocates for studies that deal with animals that live out their lives in the context of what they were actually selected to do. Given the paucity of studies from nature, it raises more questions than it answers. It focuses largely on mammals. The formation of new neurons in adult animals is a highly conserved trait in vertebrates, occurring in all groups, from fish to mammals in various brain regions. It is linked to a diversity of life history traits such as lifelong body growth in fishes and rats and seasonal variation in song control nuclei in birds (Lindsey and Tropepe 2006). In mammals, adult neurogenesis occurs physiologically in two germinal areas: the subventricular zone (SVZ), which lies adjacent to the lateral wall of...
{"title":"30 Adult Hippocampal Neurogenesis in Natural Populations of Mammals","authors":"I. Amrein, H. Lipp, R. Boonstra, J. Wojtowicz","doi":"10.1101/087969784.52.645","DOIUrl":"https://doi.org/10.1101/087969784.52.645","url":null,"abstract":"This chapter is based on the premise that if we are to acquire a deep understanding of adult neurogenesis—what it is selected for (i.e., its functional and adaptive significance), what causes it to go up or down (e.g., species constraints, reproductive hormones, seasonality, stress, and environmental conditions), and why it declines with age—the research must ultimately be grounded on an evolutionary and ecological foundation. The aphorism of Dobzansky (1973) is particularly apropos: “Nothing in biology makes sense, except in the light of evolution.” Thus, simply focusing on humans and those laboratory species we select for will not be sufficient to crack this enigma. Such a deep understanding may also aid in ameliorating debilitating aspects of the human condition after injury or in disease. This chapter advocates for studies that deal with animals that live out their lives in the context of what they were actually selected to do. Given the paucity of studies from nature, it raises more questions than it answers. It focuses largely on mammals. The formation of new neurons in adult animals is a highly conserved trait in vertebrates, occurring in all groups, from fish to mammals in various brain regions. It is linked to a diversity of life history traits such as lifelong body growth in fishes and rats and seasonal variation in song control nuclei in birds (Lindsey and Tropepe 2006). In mammals, adult neurogenesis occurs physiologically in two germinal areas: the subventricular zone (SVZ), which lies adjacent to the lateral wall of...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"49 1","pages":"645-659"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84168229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-01-01DOI: 10.1101/087969784.52.397
M. Jang, Hongjun Song, G. Ming
Active adult neurogenesis occurs from neuronal progenitor cells (NPCs) in discrete regions of the adult mammalian central nervous system (CNS) (Abrous et al. 2005; Ming and Song 2005; Lledo et al. 2006). The generation of nascent neurons from NPCs in the intact adult CNS is restricted to the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) (Alvarez-Buylla and Lim 2004). Outside of these two regions, proliferating NPCs normally generate only glia cells, but they appear to be able to give rise to neurons after insults (Emsley et al. 2005). Accumulative evidence suggests that continuous neuronal production in the adult brain under physiological conditions is involved in specific brain functions, such as olfaction, learning, and memory (Kempermann et al. 2004a). On the other hand, neural production of NPCs under pathological conditions may contribute to brain repair (Emsley et al. 2005). Functional integration of nascent neurons is achieved by progression through sequential developmental steps that resemble embryonic and fetal neurogenesis, from proliferation and fate specification of NPCs, to differentiation, migration, axonal/dendritic development, and synaptic integration of newborn neurons (Ming and Song 2005). In contrast to developing neurogenesis, adult neurogenesis arises from a significantly different environment and proceeds with concurrent activities of mature neurons within the existing circuit. Adult neurogenesis, a striking form of structural plasticity in the intact adult CNS, is dynamically regulated by many physiological and pathological stimuli (Abrous et al. 2005; Ming and Song 2005). For example, environmental enrichment (Kempermann...
成年哺乳动物中枢神经系统(CNS)离散区域的神经元祖细胞(npc)发生活跃的成年神经发生(Abrous et al. 2005;明宋2005;Lledo et al. 2006)。完整成人中枢神经系统中npc新生神经元的生成局限于侧脑室的室下区(SVZ)和海马齿状回(DG)的颗粒下区(SGZ) (Alvarez-Buylla and Lim 2004)。在这两个区域之外，增殖的npc通常只产生神经胶质细胞，但它们似乎能够在受到损伤后产生神经元(Emsley et al. 2005)。越来越多的证据表明，在生理条件下，成人大脑中连续的神经元产生与特定的大脑功能有关，如嗅觉、学习和记忆(Kempermann et al. 2004a)。另一方面，病理状态下NPCs的神经生成可能有助于大脑修复(Emsley et al. 2005)。新生神经元的功能整合是通过类似于胚胎和胎儿神经发生的顺序发育步骤来实现的，从npc的增殖和命运规范，到新生神经元的分化、迁移、轴突/树突发育和突触整合(Ming and Song 2005)。与发育中的神经发生相反，成人神经发生发生在一个明显不同的环境中，并且在现有回路中成熟神经元的同步活动中进行。成人神经发生是完整成人中枢神经系统结构可塑性的一种显著形式，受许多生理和病理刺激的动态调节(Abrous et al. 2005;Ming and Song 2005)。例如，环境富集(Kempermann…
{"title":"19 Regulation of Adult Neurogenesis by Neurotransmitters","authors":"M. Jang, Hongjun Song, G. Ming","doi":"10.1101/087969784.52.397","DOIUrl":"https://doi.org/10.1101/087969784.52.397","url":null,"abstract":"Active adult neurogenesis occurs from neuronal progenitor cells (NPCs) in discrete regions of the adult mammalian central nervous system (CNS) (Abrous et al. 2005; Ming and Song 2005; Lledo et al. 2006). The generation of nascent neurons from NPCs in the intact adult CNS is restricted to the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) (Alvarez-Buylla and Lim 2004). Outside of these two regions, proliferating NPCs normally generate only glia cells, but they appear to be able to give rise to neurons after insults (Emsley et al. 2005). Accumulative evidence suggests that continuous neuronal production in the adult brain under physiological conditions is involved in specific brain functions, such as olfaction, learning, and memory (Kempermann et al. 2004a). On the other hand, neural production of NPCs under pathological conditions may contribute to brain repair (Emsley et al. 2005). Functional integration of nascent neurons is achieved by progression through sequential developmental steps that resemble embryonic and fetal neurogenesis, from proliferation and fate specification of NPCs, to differentiation, migration, axonal/dendritic development, and synaptic integration of newborn neurons (Ming and Song 2005). In contrast to developing neurogenesis, adult neurogenesis arises from a significantly different environment and proceeds with concurrent activities of mature neurons within the existing circuit. Adult neurogenesis, a striking form of structural plasticity in the intact adult CNS, is dynamically regulated by many physiological and pathological stimuli (Abrous et al. 2005; Ming and Song 2005). For example, environmental enrichment (Kempermann...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"26 1","pages":"397-423"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81287476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-01-01DOI: 10.1101/087969752.50.725
Nina M. Muñoz, W. Grady
Transforming growth factor-β (TGF-β) family members, such as TGF-βs, activins, inhibins, bone morphogenetic proteins (BMPs), and nodal, have critical roles in the development of epithelial structures in a variety of organs, including the skin, lung, mammary gland, and gastrointestinal tract. These organs consist of cell populations derived from the ectoderm, mesoderm, and/or endoderm. The differentiation and function of cells derived from each of these three germ layers are regulated by TGF-β family members through autocrine and paracrine mechanisms, thus positioning these proteins as key regulators of organogenesis (Weaver et al. 1999; Schier 2003). The effects of TGF-β proteins are subject to autoregulatory interactions that control the activities and propagation of signaling. These effects are restricted temporally and spatially by the expression of ligands, receptors, and soluble ligand inhibitors and postreceptor signaling proteins. The roles of TGF-β family proteins in epithelial development have been deduced primarily from studies of the mammary gland, lung, and gastrointestinal tract, which are derived from the endoderm and mesoderm, and of the skin, which is from ectodermal and mesodermal origin. Furthermore, study of the epidermal appendages, specifically the teeth, hair, and feathers, has contributed to our understanding of the role of TGF-β family members in epithelial development and epithelial–mesenchymal interactions. This chapter discusses the roles of TGF-β family proteins and TGF-β signaling mediators in epithelial development in these organ systems. TGF-β family members affect the epithelium both during embryonic development and in the adult organism. In embryonic development, TGF-β, activin, and BMP-4 regulate some of...
转化生长因子-β (TGF-β)家族成员，如TGF-βs、激活素、抑制素、骨形态发生蛋白(BMPs)和结蛋白，在多种器官(包括皮肤、肺、乳腺和胃肠道)上皮结构的发育中起着关键作用。这些器官由来自外胚层、中胚层和/或内胚层的细胞群组成。TGF-β家族成员通过自分泌和旁分泌机制调节来自这三种胚层的细胞的分化和功能，从而将这些蛋白定位为器官发生的关键调节因子(Weaver et al. 1999;Schier 2003)。TGF-β蛋白的作用受控制信号活动和传播的自调节相互作用的影响。这些作用在时间和空间上受到配体、受体、可溶性配体抑制剂和受体后信号蛋白表达的限制。TGF-β家族蛋白在上皮发育中的作用主要是从乳腺、肺和胃肠道的研究中推断出来的，它们来源于内胚层和中胚层，而皮肤则来源于外胚层和中胚层。此外，对表皮附属物，特别是牙齿、毛发和羽毛的研究，有助于我们了解TGF-β家族成员在上皮发育和上皮-间质相互作用中的作用。本章讨论TGF-β家族蛋白和TGF-β信号介质在这些器官系统上皮发育中的作用。TGF-β家族成员在胚胎发育和成年生物体中都影响上皮。在胚胎发育过程中，TGF-β、激活素和BMP-4调节一些…
{"title":"23 TGF-β Family in Epithelial Development","authors":"Nina M. Muñoz, W. Grady","doi":"10.1101/087969752.50.725","DOIUrl":"https://doi.org/10.1101/087969752.50.725","url":null,"abstract":"Transforming growth factor-β (TGF-β) family members, such as TGF-βs, activins, inhibins, bone morphogenetic proteins (BMPs), and nodal, have critical roles in the development of epithelial structures in a variety of organs, including the skin, lung, mammary gland, and gastrointestinal tract. These organs consist of cell populations derived from the ectoderm, mesoderm, and/or endoderm. The differentiation and function of cells derived from each of these three germ layers are regulated by TGF-β family members through autocrine and paracrine mechanisms, thus positioning these proteins as key regulators of organogenesis (Weaver et al. 1999; Schier 2003). The effects of TGF-β proteins are subject to autoregulatory interactions that control the activities and propagation of signaling. These effects are restricted temporally and spatially by the expression of ligands, receptors, and soluble ligand inhibitors and postreceptor signaling proteins. The roles of TGF-β family proteins in epithelial development have been deduced primarily from studies of the mammary gland, lung, and gastrointestinal tract, which are derived from the endoderm and mesoderm, and of the skin, which is from ectodermal and mesodermal origin. Furthermore, study of the epidermal appendages, specifically the teeth, hair, and feathers, has contributed to our understanding of the role of TGF-β family members in epithelial development and epithelial–mesenchymal interactions. This chapter discusses the roles of TGF-β family proteins and TGF-β signaling mediators in epithelial development in these organ systems. TGF-β family members affect the epithelium both during embryonic development and in the adult organism. In embryonic development, TGF-β, activin, and BMP-4 regulate some of...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"44 1","pages":"725-759"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89518941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-01-01DOI: 10.1101/087969784.52.227
D. Lie, M. Götz
Self-renewal and proliferation of neural stem cells, neuronal fate determination of uncommitted precursors, and migration of neuroblasts are the earliest steps in adult neurogenesis. Self-renewing divisions are required for the maintenance of the stem cell pool, which ensures that neurogenesis continues throughout the lifetime of the organism. Instruction of the stem cell progeny to adopt a neuronal fate is a common feature between the neurogenic niches, yet it is likely that local instructive programs are distinct given that different neuronal phenotypes are generated in neurogenic areas. Finally, immature neurons are born distant from their future location. Thus, migration of the newborn neurons must be tightly regulated to ensure the proper integration of new mature neurons into the neuronal network. In this chapter, we discuss these processes from a functional perspective and summarize current knowledge regarding their cellular and molecular regulation. Stem cells are defined as cells with the potential to generate differentiated progeny and the potential to undergo unlimited self-renewing divisions (Weissman et al. 2001). In the hematopoietic system, the existence of adult stem cells has been proven through assays, in which a single adult cell and its progeny have been repeatedly challenged to reconstitute the entire hematopoietic system in serial transplantations to lethally irradiated organisms (Weissman et al. 2001). The reconstitution of the entire hematopoietic system demonstrates the multipotentiality of the transplanted cell, whereas their ability to do so in serial transplantations indicates the self-renewal of the initially transplanted cell. Such stringent stem cell assays are presently not available...
神经干细胞的自我更新和增殖、未固定前体的神经元命运决定以及神经母细胞的迁移是成人神经发生的最早步骤。自我更新的分裂是维持干细胞库所必需的，这确保了神经发生在生物体的整个生命周期中持续进行。干细胞后代接受神经元命运的指令是神经源性壁龛之间的共同特征，然而，考虑到不同的神经元表型在神经源性区域产生，局部指导程序可能是不同的。最后，未成熟的神经元出生时离它们未来的位置很远。因此，必须严格调节新生神经元的迁移，以确保新成熟神经元正确整合到神经元网络中。在本章中，我们从功能的角度讨论了这些过程，并总结了目前关于它们的细胞和分子调控的知识。干细胞被定义为具有产生分化后代的潜力和无限自我更新分裂的潜力的细胞(Weissman et al. 2001)。在造血系统中，成体干细胞的存在已经通过实验得到证实，在对致命辐射生物体的连续移植中，单个成体细胞及其后代被反复挑战以重建整个造血系统(Weissman et al. 2001)。整个造血系统的重建表明了移植细胞的多能性，而它们在连续移植中这样做的能力表明了最初移植细胞的自我更新。目前还没有这种严格的干细胞测定方法。
{"title":"12 Adult Neurogenesis: Similarities and Differences in Stem Cell Fate, Proliferation, Migration, and Differentiation in Distinct Forebrain Regions","authors":"D. Lie, M. Götz","doi":"10.1101/087969784.52.227","DOIUrl":"https://doi.org/10.1101/087969784.52.227","url":null,"abstract":"Self-renewal and proliferation of neural stem cells, neuronal fate determination of uncommitted precursors, and migration of neuroblasts are the earliest steps in adult neurogenesis. Self-renewing divisions are required for the maintenance of the stem cell pool, which ensures that neurogenesis continues throughout the lifetime of the organism. Instruction of the stem cell progeny to adopt a neuronal fate is a common feature between the neurogenic niches, yet it is likely that local instructive programs are distinct given that different neuronal phenotypes are generated in neurogenic areas. Finally, immature neurons are born distant from their future location. Thus, migration of the newborn neurons must be tightly regulated to ensure the proper integration of new mature neurons into the neuronal network. In this chapter, we discuss these processes from a functional perspective and summarize current knowledge regarding their cellular and molecular regulation. Stem cells are defined as cells with the potential to generate differentiated progeny and the potential to undergo unlimited self-renewing divisions (Weissman et al. 2001). In the hematopoietic system, the existence of adult stem cells has been proven through assays, in which a single adult cell and its progeny have been repeatedly challenged to reconstitute the entire hematopoietic system in serial transplantations to lethally irradiated organisms (Weissman et al. 2001). The reconstitution of the entire hematopoietic system demonstrates the multipotentiality of the transplanted cell, whereas their ability to do so in serial transplantations indicates the self-renewal of the initially transplanted cell. Such stringent stem cell assays are presently not available...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"149 1","pages":"227-265"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79437767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-01-01DOI: 10.1101/087969824.51.409
R. Weindruch, R. Colman, V. Pérez, Arlan Richardson
The classic study by McCay et al. in 1935 showed that one could increase the life span of rats by reducing their food consumption. Since this initial observation, numerous laboratories have confirmed these results and have shown that reducing food consumption 30–50% (without malnutrition) consistently increases both the mean and maximum life spans of laboratory rodents (Weindruch and Walford 1988; Masoro 2005). Caloric restriction is also able to oppose the development of diverse age-associated diseases arising in laboratory rodents, including many types of cancer, diabetes, and renal disease (Weindruch and Walford 1988). This paradigm has been termed caloric restriction, dietary restriction, or food restriction. In this chapter, we use the term caloric restriction (CR) because the decreased intake of total calories appears to be responsible for the increased life span of rodents (Masoro 2005), rather than the reduction in a specific nutrient, such as dietary protein or fat (Iwasaki et al. 1988; Masoro et al. 1989). It is important to note that the effect of CR on longevity is not limited to rodents, as it increases the life span of a variety of invertebrates, e.g., yeast, Caenorhabditis elegans , and Drosophila (Min and Tatar 2006), as well as of dogs (Kealy et al. 2002). In this review chapter, we focus on what currently is known of the biological mechanism responsible for the life-extending action of CR in mammals, specifically laboratory rodents and nonhuman primates. LABORATORY RODENTS Since the seminal observation by McCay et al. in 1935, CR has been shown...
McCay等人在1935年的经典研究表明，可以通过减少老鼠的食物消耗来延长它们的寿命。自最初的观察以来，许多实验室已经证实了这些结果，并表明减少食物消耗30-50%(没有营养不良)持续增加实验室啮齿动物的平均寿命和最长寿命(Weindruch和Walford 1988;Masoro 2005)。热量限制还能够防止实验室啮齿动物出现各种与年龄相关的疾病，包括许多类型的癌症、糖尿病和肾脏疾病(Weindruch和Walford 1988)。这种模式被称为热量限制、饮食限制或食物限制。在本章中，我们使用了热量限制(CR)这个术语，因为总热量摄入的减少似乎是啮齿动物寿命延长的原因(Masoro 2005)，而不是特定营养素(如膳食蛋白质或脂肪)的减少(Iwasaki et al. 1988;Masoro et al. 1989)。值得注意的是，CR对寿命的影响并不局限于啮齿类动物，因为它可以延长多种无脊椎动物的寿命，例如酵母、秀丽隐杆线虫和果蝇(Min and tatatar 2006)，以及狗(Kealy et al. 2002)。在本综述章节中，我们将重点介绍目前已知的CR在哺乳动物(特别是实验室啮齿动物和非人灵长类动物)中延长寿命的生物学机制。自1935年McCay等人的开创性观察以来，CR已被证明…
{"title":"15 How Does Caloric Restriction Increase the Longevity of Mammals","authors":"R. Weindruch, R. Colman, V. Pérez, Arlan Richardson","doi":"10.1101/087969824.51.409","DOIUrl":"https://doi.org/10.1101/087969824.51.409","url":null,"abstract":"The classic study by McCay et al. in 1935 showed that one could increase the life span of rats by reducing their food consumption. Since this initial observation, numerous laboratories have confirmed these results and have shown that reducing food consumption 30–50% (without malnutrition) consistently increases both the mean and maximum life spans of laboratory rodents (Weindruch and Walford 1988; Masoro 2005). Caloric restriction is also able to oppose the development of diverse age-associated diseases arising in laboratory rodents, including many types of cancer, diabetes, and renal disease (Weindruch and Walford 1988). This paradigm has been termed caloric restriction, dietary restriction, or food restriction. In this chapter, we use the term caloric restriction (CR) because the decreased intake of total calories appears to be responsible for the increased life span of rodents (Masoro 2005), rather than the reduction in a specific nutrient, such as dietary protein or fat (Iwasaki et al. 1988; Masoro et al. 1989). It is important to note that the effect of CR on longevity is not limited to rodents, as it increases the life span of a variety of invertebrates, e.g., yeast, Caenorhabditis elegans , and Drosophila (Min and Tatar 2006), as well as of dogs (Kealy et al. 2002). In this review chapter, we focus on what currently is known of the biological mechanism responsible for the life-extending action of CR in mammals, specifically laboratory rodents and nonhuman primates. LABORATORY RODENTS Since the seminal observation by McCay et al. in 1935, CR has been shown...","PeriodicalId":10493,"journal":{"name":"Cold Spring Harbor Monograph Archive","volume":"33 1","pages":"409-425"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73115513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：