Pub Date : 2024-10-04DOI: 10.1016/j.ydbio.2024.09.015
Catarina Dias, Rui Dilão
We modelled and calibrated the distributions of the seven-stripe patterns of Even-skipped (Eve) and Fushi-tarazu (Ftz) pair-rule proteins along the anteroposterior axis of the Drosphila embryo, established during early development. We have identified the putative repressive combinations for five Eve enhancers, and we have explored the relationship between Eve and Ftz for complementary patterns. The regulators of Eve and Ftz are stripe-specific DNA enhancers with embryo position-dependent activation rates and are regulated by the gap family of proteins. We achieved remarkable data matching of the Eve stripe pattern, and the calibrated model reproduces gap gene mutation experiments. Extended work inferring the Wingless (Wg) fourteen stripe pattern from Eve and Ftz enhancers have been proposed, clarifying the hierarchical structure of Drosphila's genetic expression network during early development.
我们模拟并校准了在早期发育过程中建立的 Even-skipped（夏娃）和 Fushi-tarazu（Ftz）成对规则蛋白沿 Drosphila 胚胎前后轴的七条纹图案的分布。我们确定了五个夏娃增强子的推定抑制组合，并探索了夏娃和 Ftz 之间的互补模式关系。夏娃和 Ftz 的调控因子是条纹特异性 DNA 增强子，其激活率与胚胎位置有关，并受缺口蛋白家族的调控。我们实现了夏娃条纹模式的显著数据匹配，校准后的模型重现了间隙基因突变实验。我们提出了从 Eve 和 Ftz 增强子推断无翼虫（Wg）14 条纹模式的扩展工作，从而阐明了 Drosphila 早期发育过程中基因表达网络的层次结构。
{"title":"Modelling and calibration of pair-rule protein patterns in Drosophila embryo: From Even-skipped and Fushi-tarazu to Wingless expression networks","authors":"Catarina Dias, Rui Dilão","doi":"10.1016/j.ydbio.2024.09.015","DOIUrl":"10.1016/j.ydbio.2024.09.015","url":null,"abstract":"<div><div>We modelled and calibrated the distributions of the seven-stripe patterns of Even-skipped (<em>Eve</em>) and Fushi-tarazu (<em>Ftz</em>) pair-rule proteins along the anteroposterior axis of the <em>Drosphila</em> embryo, established during early development. We have identified the putative repressive combinations for five <em>Eve</em> enhancers, and we have explored the relationship between <em>Eve</em> and <em>Ftz</em> for complementary patterns. The regulators of <em>Eve</em> and <em>Ftz</em> are stripe-specific DNA enhancers with embryo position-dependent activation rates and are regulated by the gap family of proteins. We achieved remarkable data matching of the <em>Eve</em> stripe pattern, and the calibrated model reproduces gap gene mutation experiments. Extended work inferring the Wingless (<em>Wg</em>) fourteen stripe pattern from <em>Eve</em> and <em>Ftz</em> enhancers have been proposed, clarifying the hierarchical structure of <em>Drosphila</em>'s genetic expression network during early development.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-02DOI: 10.1016/j.ydbio.2024.09.016
Emma Kristine Beard, Rachael P. Norris, Miki Furusho, Mark Terasaki, Mayu Inaba
In the Drosophila testis, developing germ cells are encapsulated by somatic support cells throughout development. Soma-germline interactions are essential for successful spermiogenesis. However, it is still not fully understood what signaling events take place between the soma and the germline. In this study, we found that a Bone Morphogenetic Protein (BMP) ligand, Glass bottom boat (Gbb), secreted from somatic cyst cells (CCs), signals to differentiating germ cells to maintain proper spermiogenesis. Knockdown of Gbb in CCs or the type I BMP receptor Saxophone (Sax) in germ cells leads to a defect in sperm head bundling and decreased fertility. Our Transmission Electron Microscopy (TEM) analyses revealed that the mutant germ cells have aberrant morphology of mitochondria throughout the stages of spermiogenesis and exhibit a defect in nebenkern formation. Elongating spermatids show uncoupled nuclei and elongating mitochondrial derivatives, suggesting that improper mitochondrial development may cause sperm bundling defects. Taken together, we propose a new role of soma-derived BMP signaling, which is essential for spermiogenesis.
{"title":"Soma-to-germline BMP signal is essential for Drosophila spermiogenesis","authors":"Emma Kristine Beard, Rachael P. Norris, Miki Furusho, Mark Terasaki, Mayu Inaba","doi":"10.1016/j.ydbio.2024.09.016","DOIUrl":"10.1016/j.ydbio.2024.09.016","url":null,"abstract":"<div><div>In the <em>Drosophila</em> testis, developing germ cells are encapsulated by somatic support cells throughout development. Soma-germline interactions are essential for successful spermiogenesis. However, it is still not fully understood what signaling events take place between the soma and the germline. In this study, we found that a Bone Morphogenetic Protein (BMP) ligand, Glass bottom boat (Gbb), secreted from somatic cyst cells (CCs), signals to differentiating germ cells to maintain proper spermiogenesis. Knockdown of Gbb in CCs or the type I BMP receptor Saxophone (Sax) in germ cells leads to a defect in sperm head bundling and decreased fertility. Our Transmission Electron Microscopy (TEM) analyses revealed that the mutant germ cells have aberrant morphology of mitochondria throughout the stages of spermiogenesis and exhibit a defect in nebenkern formation. Elongating spermatids show uncoupled nuclei and elongating mitochondrial derivatives, suggesting that improper mitochondrial development may cause sperm bundling defects. Taken together, we propose a new role of soma-derived BMP signaling, which is essential for spermiogenesis.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.ydbio.2024.09.014
Khulganaa Buyannemekh , Paul Villoutreix , Vincent Bertrand
While the nervous system of bilaterian animals is mainly left-right (L-R) symmetric at the anatomical level, some molecular and functional L-R asymmetries exist. However, the extent of these molecular asymmetries and their functional consequences remain poorly characterized. C. elegans allows to study L-R asymmetries in the nervous system with single-neuron resolution. We have previously shown that a neural bHLH transcription factor, HLH-16/Olig, is L-R asymmetrically expressed in the AIY neuron lineage and regulates AIY axon projections in a L-R asymmetric manner. Here, by combining a candidate approach and single-cell RNA sequencing data analysis, we identify the ephrin protein EFN-2 and the Flamingo protein FMI-1 as downstream targets of HLH-16 that are L-R asymmetrically expressed in the AIY lineage. We show that EFN-2 and FMI-1 collaborate in the L-R asymmetric regulation of axonal growth. EFN-2 may act via a non-canonical receptor of the L1CAM family, SAX-7. Our study reveals novel molecular L-R asymmetries in the C. elegans nervous system and their functional consequences.
{"title":"Left/right asymmetrically expressed ephrin and Flamingo proteins regulate lateralized axon growth in C. elegans","authors":"Khulganaa Buyannemekh , Paul Villoutreix , Vincent Bertrand","doi":"10.1016/j.ydbio.2024.09.014","DOIUrl":"10.1016/j.ydbio.2024.09.014","url":null,"abstract":"<div><div>While the nervous system of bilaterian animals is mainly left-right (L-R) symmetric at the anatomical level, some molecular and functional L-R asymmetries exist. However, the extent of these molecular asymmetries and their functional consequences remain poorly characterized. <em>C. elegans</em> allows to study L-R asymmetries in the nervous system with single-neuron resolution. We have previously shown that a neural bHLH transcription factor, HLH-16/Olig, is L-R asymmetrically expressed in the AIY neuron lineage and regulates AIY axon projections in a L-R asymmetric manner. Here, by combining a candidate approach and single-cell RNA sequencing data analysis, we identify the ephrin protein EFN-2 and the Flamingo protein FMI-1 as downstream targets of HLH-16 that are L-R asymmetrically expressed in the AIY lineage. We show that EFN-2 and FMI-1 collaborate in the L-R asymmetric regulation of axonal growth. EFN-2 may act via a non-canonical receptor of the L1CAM family, SAX-7. Our study reveals novel molecular L-R asymmetries in the <em>C. elegans</em> nervous system and their functional consequences.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.ydbio.2024.09.013
Ching-Hsin Yang , Yan-wei Wang , Chen-wei Hsu , Bon-chu Chung
Zebrafish sex differentiation is a complicated process and the detailed mechanism has not been fully understood. Here we characterized a transcription factor, Foxl2l, which participates in female oogenesis. We show that it is expressed specifically in proliferating germ cells in juvenile gonads and mature ovaries. We have used CRISPR-Cas9 to generate zebrafish deficient in foxl2l expression. Zebrafish with foxl2l−/− are all males, and this female-to-male sex reversal cannot be reversed by tp53 mutation, indicating this sex reversal is unrelated to cell death. We have generated transgenic fish expressing GFP under the control of foxl2l promoter to track the development of foxl2l + -germ cells; these cells failed to enter meiosis and accumulated as cystic cells in the foxl2l−/− mutant. Our RNA-seq analysis also showed the reduced expression of genes in meiosis and oogenesis among other affected pathways. All together, we show that zebrafish Foxl2l is a nuclear factor controlling the expression of meiotic and oogenic genes, and its deficiency leads to defective meiotic entry and the accumulation of premeiotic germ cells.
{"title":"Zebrafish Foxl2l functions in proliferating germ cells for female meiotic entry","authors":"Ching-Hsin Yang , Yan-wei Wang , Chen-wei Hsu , Bon-chu Chung","doi":"10.1016/j.ydbio.2024.09.013","DOIUrl":"10.1016/j.ydbio.2024.09.013","url":null,"abstract":"<div><div>Zebrafish sex differentiation is a complicated process and the detailed mechanism has not been fully understood. Here we characterized a transcription factor, Foxl2l, which participates in female oogenesis. We show that it is expressed specifically in proliferating germ cells in juvenile gonads and mature ovaries. We have used CRISPR-Cas9 to generate zebrafish deficient in <em>foxl2l</em> expression. Zebrafish with <em>foxl2l</em><sup><em>−/−</em></sup> are all males, and this female-to-male sex reversal cannot be reversed by <em>tp53</em> mutation, indicating this sex reversal is unrelated to cell death. We have generated transgenic fish expressing GFP under the control of <em>foxl2l</em> promoter to track the development of <em>foxl2l</em> + -germ cells; these cells failed to enter meiosis and accumulated as cystic cells in the <em>foxl2l</em><sup><em>−/−</em></sup> mutant. Our RNA-seq analysis also showed the reduced expression of genes in meiosis and oogenesis among other affected pathways. All together, we show that zebrafish Foxl2l is a nuclear factor controlling the expression of meiotic and oogenic genes, and its deficiency leads to defective meiotic entry and the accumulation of premeiotic germ cells.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25DOI: 10.1016/j.ydbio.2024.09.009
Whitney Roberson, Jorden N. Holland, Bruce B. Riley
During inner ear development, specification of sensory epithelia requires dynamic regulation of Fgf signaling. In zebrafish, high levels of Fgf are necessary and sufficient to specify the utricular/vestibular macula, whereas the saccular/auditory macula requires a discreet lower level of Fgf. Transcription factors Pax2a and Pax5 act downstream of Fgf to help specify utricular identity, loss of which leads to sporadic extrusion of hair cells from the utricular macula. The mechanism for utricular instability is not clear but is potentially related to reduced expression of cdh1/Ecad caused by disruption of pax2a. Here we find that utricular hair cells in pax2−/− and pax5−/− mutants gradually lose adhesive contact with the macula, leading to ejection of intact hair cells from either the basal or apical surface. The phenotype is far more severe in pax2a−/− mutants and is progressive, resulting in loss of large swaths of the utricular hair cells by 82 hpf. Instability is caused by elevated Fgf signaling in the utricle, as modest reduction of Fgf signaling with a low dose of SU5402 prevents hair cell loss in pax2a−/− mutants. Misexpression of cdh1/Ecad in pax2a−/− mutants partially rescues pax2a−/− mutants. Elevating β-catenin levels by treatment with BIO, or misexpression of a mutant form of β-catenin lacking transcriptional activity but retaining cell adhesion function, fully rescues pax2a−/− mutants. In contrast, Wnt signaling is not required for utricular stability. Thus, Pax2/5 factors serve to counteract the destabilizing effects of elevated Fgf signaling needed to specify utricular identity.
{"title":"Pax2a, Pax5 and Cdh1-β-catenin, but not Wnt, protect sensory hair cells from destabilizing effects of fgf signaling on cell adhesion","authors":"Whitney Roberson, Jorden N. Holland, Bruce B. Riley","doi":"10.1016/j.ydbio.2024.09.009","DOIUrl":"10.1016/j.ydbio.2024.09.009","url":null,"abstract":"<div><div>During inner ear development, specification of sensory epithelia requires dynamic regulation of Fgf signaling. In zebrafish, high levels of Fgf are necessary and sufficient to specify the utricular/vestibular macula, whereas the saccular/auditory macula requires a discreet lower level of Fgf. Transcription factors Pax2a and Pax5 act downstream of Fgf to help specify utricular identity, loss of which leads to sporadic extrusion of hair cells from the utricular macula. The mechanism for utricular instability is not clear but is potentially related to reduced expression of <em>cdh1/Ecad</em> caused by disruption of <em>pax2a</em>. Here we find that utricular hair cells in <em>pax2−/−</em> and <em>pax5−/−</em> mutants gradually lose adhesive contact with the macula, leading to ejection of intact hair cells from either the basal or apical surface. The phenotype is far more severe in <em>pax2a−/−</em> mutants and is progressive, resulting in loss of large swaths of the utricular hair cells by 82 hpf. Instability is caused by elevated Fgf signaling in the utricle, as modest reduction of Fgf signaling with a low dose of SU5402 prevents hair cell loss in <em>pax2a−/−</em> mutants. Misexpression of <em>cdh1/Ecad</em> in <em>pax2a−/−</em> mutants partially rescues <em>pax2a−/−</em> mutants. Elevating β-catenin levels by treatment with BIO, or misexpression of a mutant form of β-catenin lacking transcriptional activity but retaining cell adhesion function, fully rescues <em>pax2a−/−</em> mutants. In contrast, Wnt signaling is not required for utricular stability. Thus, Pax2/5 factors serve to counteract the destabilizing effects of elevated Fgf signaling needed to specify utricular identity.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-24DOI: 10.1016/j.ydbio.2024.09.011
Carole Desmarquet-Trin Dinh, Marie Manceau
From feather and hair dotted arrays to pigmented stripes and spots, the spatial distribution of skin appendages and colouration often forms visible ornaments crucial for fitness in the coat of birds and mammals. These geometrical motifs are extremely diverse in nature. Yet, phenotypic surveys evidenced common themes in variation: the orientation, appendage-specificity or pigmentation of a given region may be conserved across groups or species. Here, we review naturalist observations of natural variation in the anatomy and ecological function of the skin pattern in amniotes. We then describe several decades of genetics, mathematical modelling and experimental embryology work aiming at understanding the molecular and morphogenetic mechanisms responsible for pattern formation. We discuss how these studies provided evidence that the morphological trends and differences representative of the phenotypic landscape of skin patterns in wild amniote species is rooted in the mechanisms controlling the production of distinct compartments in the embryonic skin.
{"title":"Structure, function and formation of the amniote skin pattern","authors":"Carole Desmarquet-Trin Dinh, Marie Manceau","doi":"10.1016/j.ydbio.2024.09.011","DOIUrl":"10.1016/j.ydbio.2024.09.011","url":null,"abstract":"<div><div>From feather and hair dotted arrays to pigmented stripes and spots, the spatial distribution of skin appendages and colouration often forms visible ornaments crucial for fitness in the coat of birds and mammals. These geometrical motifs are extremely diverse in nature. Yet, phenotypic surveys evidenced common themes in variation: the orientation, appendage-specificity or pigmentation of a given region may be conserved across groups or species. Here, we review naturalist observations of natural variation in the anatomy and ecological function of the skin pattern in amniotes. We then describe several decades of genetics, mathematical modelling and experimental embryology work aiming at understanding the molecular and morphogenetic mechanisms responsible for pattern formation. We discuss how these studies provided evidence that the morphological trends and differences representative of the phenotypic landscape of skin patterns in wild amniote species is rooted in the mechanisms controlling the production of distinct compartments in the embryonic skin.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-21DOI: 10.1016/j.ydbio.2024.09.008
Elliot A. Perens , Deborah Yelon
Proper organ formation depends on the precise delineation of organ territories containing defined numbers of progenitor cells. Kidney progenitors reside in bilateral stripes of posterior mesoderm that are referred to as the intermediate mesoderm (IM). Previously, we showed that the transcription factors Hand2 and Osr1 act to strike a balance between the specification of the kidney progenitors in the IM and the vessel progenitors in the laterally adjacent territory. Recently, the transcription factor Npas4l – an early and essential driver of vessel and blood progenitor formation – was shown to inhibit kidney development. Here we demonstrate how kidney progenitor specification is coordinated by hand2, osr1, and npas4l. We find that npas4l and the IM marker pax2a are transiently co-expressed in the posterior lateral mesoderm, and npas4l is necessary to inhibit IM formation. Consistent with the expression of npas4l flanking the medial and lateral sides of the IM, our findings suggest roles for npas4l in defining the IM boundaries at each of these borders. At the lateral IM border, hand2 promotes and osr1 inhibits the formation of npas4l-expressing lateral vessel progenitors, and hand2 requires npas4l to inhibit IM formation and to promote vessel formation. Meanwhile, npas4l appears to have an additional role in suppressing IM fate at the medial border: npas4l loss-of-function enhances hand2 mutant IM defects and results in excess IM generated outside of the lateral hand2-expressing territory. Together, our findings reveal that establishment of the medial and lateral boundaries of the IM requires inhibition of kidney progenitor specification by the neighboring drivers of vessel progenitor fate.
器官的正确形成取决于器官区域的精确划分，这些区域包含数量明确的祖细胞。肾脏祖细胞位于被称为中间中胚层（IM）的后中胚层的双侧条带中。此前，我们曾发现转录因子 Hand2 和 Osr1 在中间层肾脏祖细胞和侧邻区域血管祖细胞的规格化之间起到平衡作用。最近，转录因子Npas4l--血管和血液祖细胞形成的早期重要驱动因子--被证明会抑制肾脏的发育。在这里，我们证明了肾脏祖细胞的分化是如何通过 hand2、osr1 和 npas4l 协调的。我们发现 npas4l 和 IM 标记 pax2a 在后侧中胚层瞬时共表达，并且 npas4l 是抑制 IM 形成所必需的。我们的研究结果表明，npas4l 在 IM 的内侧和外侧均有表达，这与 npas4l 在 IM 内侧和外侧边界的表达一致。在IM外侧边界，hand2促进而osr1抑制表达npas4l的外侧血管祖细胞的形成，hand2需要npas4l来抑制IM的形成并促进血管的形成。同时，npas4l 在抑制内侧边界 IM 的命运方面似乎还有另外一个作用：npas4l 功能缺失会增强 hand2 突变体 IM 的缺陷，并导致在 hand2 表达的外侧区域之外产生过多的 IM。总之，我们的研究结果表明，IM 内侧和外侧边界的建立需要血管祖细胞命运的邻近驱动因子对肾脏祖细胞规范的抑制。
{"title":"Drivers of vessel progenitor fate define intermediate mesoderm dimensions by inhibiting kidney progenitor specification","authors":"Elliot A. Perens , Deborah Yelon","doi":"10.1016/j.ydbio.2024.09.008","DOIUrl":"10.1016/j.ydbio.2024.09.008","url":null,"abstract":"<div><div>Proper organ formation depends on the precise delineation of organ territories containing defined numbers of progenitor cells. Kidney progenitors reside in bilateral stripes of posterior mesoderm that are referred to as the intermediate mesoderm (IM). Previously, we showed that the transcription factors Hand2 and Osr1 act to strike a balance between the specification of the kidney progenitors in the IM and the vessel progenitors in the laterally adjacent territory. Recently, the transcription factor Npas4l – an early and essential driver of vessel and blood progenitor formation – was shown to inhibit kidney development. Here we demonstrate how kidney progenitor specification is coordinated by <em>hand2</em>, <em>osr1</em>, and <em>npas4l</em>. We find that <em>npas4l</em> and the IM marker <em>pax2a</em> are transiently co-expressed in the posterior lateral mesoderm, and <em>npas4l</em> is necessary to inhibit IM formation. Consistent with the expression of <em>npas4l</em> flanking the medial and lateral sides of the IM, our findings suggest roles for <em>npas4l</em> in defining the IM boundaries at each of these borders. At the lateral IM border, <em>hand2</em> promotes and <em>osr1</em> inhibits the formation of <em>npas4l</em>-expressing lateral vessel progenitors, and <em>hand2</em> requires <em>npas4l</em> to inhibit IM formation and to promote vessel formation. Meanwhile, <em>npas4l</em> appears to have an additional role in suppressing IM fate at the medial border: <em>npas4l</em> loss-of-function enhances <em>hand2</em> mutant IM defects and results in excess IM generated outside of the lateral <em>hand2</em>-expressing territory. Together, our findings reveal that establishment of the medial and lateral boundaries of the IM requires inhibition of kidney progenitor specification by the neighboring drivers of vessel progenitor fate.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
During anuran metamorphosis from herbivorous tadpoles to carnivorous frogs, the gastrointestinal (GI) tract undergoes drastic remodeling, such as the formation of the stomach-intestine boundary and the development of the pyloric sphincter at the posterior end of the stomach. However, the morphogenetic process and molecular mechanisms of how the pyloric sphincter is formed during metamorphosis, instead of during embryogenesis as in amniotes, are largely uninvestigated. Using the African clawed frog Xenopus laevis, we histologically examined the development of the pylorus region from embryonic to froglet stages and performed spatiotemporal gene expression analyses. We found that the pyloric sphincter is formed at a flexure within the pyloric region during metamorphic climax, and that the pyloric and duodenal epithelia, which are morphologically indistinguishable before sphincter formation, become clearly demarcated by the sphincter at the end of metamorphosis. Consistent with these morphological changes, expression domains of a stomach marker barx1 and an intestine marker cdx2 overlapped until late metamorphic climax, but became separated after metamorphosis. Despite the absence of the sphincter before metamorphosis, various genes crucial for sphincter formation in amniotes were already expressed in the pylorus region of Xenopus embryos. RNA-sequencing analysis at pre-metamorphic and metamorphic-climax stages suggest unappreciated roles of genes, such as those for retinoic acid signaling and various transcription factors, in suppressing or promoting sphincter formation. These data provide histological and molecular insights into the heterochrony of the pyloric sphincter formation in amniotes and anurans.
{"title":"Histological and gene-expression analyses of pyloric sphincter formation during stomach metamorphosis in Xenopus laevis","authors":"Kei Nagura , Takafumi Ikeda , Takashi Hasebe , Yumeko Satou-Kobayashi , Sumio Udagawa , Shuji Shigenobu , Atsuko Ishizuya-Oka , Masanori Taira","doi":"10.1016/j.ydbio.2024.09.010","DOIUrl":"10.1016/j.ydbio.2024.09.010","url":null,"abstract":"<div><div>During anuran metamorphosis from herbivorous tadpoles to carnivorous frogs, the gastrointestinal (GI) tract undergoes drastic remodeling, such as the formation of the stomach-intestine boundary and the development of the pyloric sphincter at the posterior end of the stomach. However, the morphogenetic process and molecular mechanisms of how the pyloric sphincter is formed during metamorphosis, instead of during embryogenesis as in amniotes, are largely uninvestigated. Using the African clawed frog <em>Xenopus laevis</em>, we histologically examined the development of the pylorus region from embryonic to froglet stages and performed spatiotemporal gene expression analyses. We found that the pyloric sphincter is formed at a flexure within the pyloric region during metamorphic climax, and that the pyloric and duodenal epithelia, which are morphologically indistinguishable before sphincter formation, become clearly demarcated by the sphincter at the end of metamorphosis. Consistent with these morphological changes, expression domains of a stomach marker <em>barx1</em> and an intestine marker <em>cdx2</em> overlapped until late metamorphic climax, but became separated after metamorphosis. Despite the absence of the sphincter before metamorphosis, various genes crucial for sphincter formation in amniotes were already expressed in the pylorus region of <em>Xenopus</em> embryos. RNA-sequencing analysis at pre-metamorphic and metamorphic-climax stages suggest unappreciated roles of genes, such as those for retinoic acid signaling and various transcription factors, in suppressing or promoting sphincter formation. These data provide histological and molecular insights into the heterochrony of the pyloric sphincter formation in amniotes and anurans.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immature oocytes enclosed in primordial follicles stored in female ovaries are under constant threat of DNA damage induced by endogenous and exogenous factors. Checkpoint kinase 2 (CHEK2) is a key mediator of the DNA damage response (DDR) in all cells. Genetic studies have shown that CHEK2 and its downstream targets, p53, and TAp63, regulate primordial follicle elimination in response to DNA damage. However, the mechanism leading to their demise is still poorly characterized. Single-cell and bulk RNA sequencing were used to determine the DDR in wild-type and Chek2-deficient ovaries. A low but oocyte-lethal dose of ionizing radiation induces ovarian DDR that is solely dependent on CHEK2. DNA damage activates multiple response pathways related to apoptosis, p53, interferon signaling, inflammation, cell adhesion, and intercellular communication. These pathways are differentially employed by different ovarian cell types, with oocytes disproportionately affected by radiation. Novel genes and pathways are induced by radiation specifically in oocytes, shedding light on their sensitivity to DNA damage, and implicating a coordinated response between oocytes and pregranulosa cells within the follicle. These findings provide a foundation for future studies on the specific mechanisms regulating oocyte survival in the context of aging, therapeutic and environmental genotoxic exposures.
储存在女性卵巢原始卵泡中的未成熟卵母细胞不断受到内源性和外源性因素诱导的 DNA 损伤的威胁。检查点激酶2（CHEK2）是所有细胞中DNA损伤反应（DDR）的关键介质。遗传学研究表明，CHEK2 及其下游靶标 p53 和 TAp63 在 DNA 损伤反应中调节原始卵泡的消亡。然而，导致原始卵泡消亡的机制仍不甚明了。研究人员利用单细胞和大量RNA测序来确定野生型和Chek2缺陷型卵巢的DDR。低剂量但卵母细胞致死的电离辐射诱导卵巢DDR完全依赖于CHEK2。DNA 损伤会激活与细胞凋亡、p53、干扰素信号、炎症、细胞粘附和细胞间通讯有关的多种反应途径。不同类型的卵巢细胞采用不同的途径，其中卵母细胞受辐射的影响尤为严重。新的基因和途径在卵母细胞中受到辐射的特异性诱导，揭示了卵母细胞对DNA损伤的敏感性，并暗示了卵母细胞和卵泡内前颗粒细胞之间的协调反应。这些发现为今后研究在衰老、治疗和环境基因毒性暴露的背景下调节卵母细胞存活的具体机制奠定了基础。
{"title":"Single-cell and bulk transcriptional profiling of mouse ovaries reveals novel genes and pathways associated with DNA damage response in oocytes","authors":"Monique Mills , Chihiro Emori , Parveen Kumar , Zachary Boucher , Joshy George , Ewelina Bolcun-Filas","doi":"10.1016/j.ydbio.2024.09.007","DOIUrl":"10.1016/j.ydbio.2024.09.007","url":null,"abstract":"<div><div>Immature oocytes enclosed in primordial follicles stored in female ovaries are under constant threat of DNA damage induced by endogenous and exogenous factors. Checkpoint kinase 2 (CHEK2) is a key mediator of the DNA damage response (DDR) in all cells. Genetic studies have shown that CHEK2 and its downstream targets, p53, and TAp63, regulate primordial follicle elimination in response to DNA damage. However, the mechanism leading to their demise is still poorly characterized. Single-cell and bulk RNA sequencing were used to determine the DDR in wild-type and <em>Chek2</em>-deficient ovaries. A low but oocyte-lethal dose of ionizing radiation induces ovarian DDR that is solely dependent on CHEK2. DNA damage activates multiple response pathways related to apoptosis, p53, interferon signaling, inflammation, cell adhesion, and intercellular communication. These pathways are differentially employed by different ovarian cell types, with oocytes disproportionately affected by radiation. Novel genes and pathways are induced by radiation specifically in oocytes, shedding light on their sensitivity to DNA damage, and implicating a coordinated response between oocytes and pregranulosa cells within the follicle. These findings provide a foundation for future studies on the specific mechanisms regulating oocyte survival in the context of aging, therapeutic and environmental genotoxic exposures.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1016/j.ydbio.2024.09.006
Zhiyu Mu , Pengfei Zheng , Shuangyu Liu , Yunsi Kang , Haibo Xie
PLK4 plays a crucial role in centriole duplication, which is essential for maintaining cellular processes such as cell division, cytoskeletal stability, and cilia formation. However, the mechanisms of PLK4 remain incompletely understood, especially in the embryonic development of vertebrate species. In this study, we observed that Plk4 dysfunction led to abnormal embryonic development in zebrafish, characterized by symptoms such as dark and wrinkled skin, microphthalmia, and body axis curvature. In plk4 mutants, defects in centriole duplication led to abnormal cell division, apoptosis, and ciliogenesis defects. Moreover, overexpression of plk4 in zebrafish embryos caused excessive centrosome amplification, disrupting embryonic gastrulation through abnormal cell division and ultimately resulting in embryonic lethality. Furthermore, we identified the "cryptic" polo box (CPB) domain, consisting of two PBs (PB1 and PB2), as the critical centrosome localization domain of Plk4. Surprisingly, overexpression of these two PB domains alone was sufficient to induce embryonic lethality. Additionally, we discovered a truncated form of CPB that localizes to the centrosome without causing defects in embryonic development. Our results demonstrate that Plk4 tightly controls centriole duplication, which is essential for early embryonic development in zebrafish.
{"title":"Plk4 regulates centriole duplication in the embryonic development of zebrafish","authors":"Zhiyu Mu , Pengfei Zheng , Shuangyu Liu , Yunsi Kang , Haibo Xie","doi":"10.1016/j.ydbio.2024.09.006","DOIUrl":"10.1016/j.ydbio.2024.09.006","url":null,"abstract":"<div><div>PLK4 plays a crucial role in centriole duplication, which is essential for maintaining cellular processes such as cell division, cytoskeletal stability, and cilia formation. However, the mechanisms of PLK4 remain incompletely understood, especially in the embryonic development of vertebrate species. In this study, we observed that Plk4 dysfunction led to abnormal embryonic development in zebrafish, characterized by symptoms such as dark and wrinkled skin, microphthalmia, and body axis curvature. In <em>plk4</em> mutants, defects in centriole duplication led to abnormal cell division, apoptosis, and ciliogenesis defects. Moreover, overexpression of <em>plk4</em> in zebrafish embryos caused excessive centrosome amplification, disrupting embryonic gastrulation through abnormal cell division and ultimately resulting in embryonic lethality. Furthermore, we identified the \"cryptic\" polo box (CPB) domain, consisting of two PBs (PB1 and PB2), as the critical centrosome localization domain of Plk4. Surprisingly, overexpression of these two PB domains alone was sufficient to induce embryonic lethality. Additionally, we discovered a truncated form of CPB that localizes to the centrosome without causing defects in embryonic development. Our results demonstrate that Plk4 tightly controls centriole duplication, which is essential for early embryonic development in zebrafish.</div></div>","PeriodicalId":11070,"journal":{"name":"Developmental biology","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142281784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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