Wiley Interdisciplinary Reviews: Developmental Biology最新文献

Lifelong generation of blood and immune cells depends on hematopoietic stem cells (HSCs). Their function is precisely regulated by complex molecular networks that integrate and respond to ever changing physiological demands of the body. Over the past several years, significant advances have been made in understanding the extrinsic regulation of HSCs during development and in homeostasis. Propelled by technical advances in the field, the cellular and molecular components of the microenvironment that support HSCs in vivo are emerging. In addition, the interaction of HSCs with their niches is appreciated as a critical contributor to the pathogenesis of a number of hematologic disorders. Here, we review these advances in detail and highlight the extrinsic regulation of HSCs in the context of development, homeostasis, and diseases. WIREs Dev Biol 2017, 6:e279. doi: 10.1002/wdev.279 For further resources related to this article, please visit the WIREs website.

Organisms are often capable of modifying their development to better suit their environment. Under adverse conditions, the nematode Caenorhabditis elegans develops into a stress-resistant alternative larval stage called dauer. The dauer stage is the primary survival stage for C. elegans in nature. Large-scale tissue remodeling during dauer conveys resistance to harsh environments. The environmental and genetic regulation of the decision to enter dauer has been extensively studied. However, less is known about the mechanisms regulating tissue remodeling. Changes to the cuticle and suppression of feeding in dauers lead to an increased resistance to external stressors. Meanwhile reproductive development arrests during dauer while preserving the ability to reproduce once favorable environmental conditions return. Dramatic remodeling of neurons, glia, and muscles during dauer likely facilitate dauer-specific behaviors. Dauer-specific pulsation of the excretory duct likely mediates a response to osmotic stress. The power of C. elegans genetics has uncovered some of the molecular pathways regulating dauer tissue remodeling. In addition to genes that regulate single remodeling events, several mutants result in pleiotropic defects in dauer remodeling. This review details the individual aspects of morphological changes that occur during dauer formation and discusses molecular mechanisms regulating these processes. The dauer stage provides us with an excellent model for understanding phenotypic plasticity and remodeling from the individual cell to an entire animal. WIREs Dev Biol 2017, 6:e278. doi: 10.1002/wdev.278 For further resources related to this article, please visit the WIREs website.

A mouth is present in all animals, and comprises an opening from the outside into the oral cavity and the beginnings of the digestive tract to allow eating. This review focuses on the earliest steps in mouth formation. In the first half, we conclude that the mouth arose once during evolution. In all animals, the mouth forms from ectoderm and endoderm. A direct association of oral ectoderm and digestive endoderm is present even in triploblastic animals, and in chordates, this region is known as the extreme anterior domain (EAD). Further support for a single origin of the mouth is a conserved set of genes that form a 'mouth gene program' including foxA and otx2. In the second half of this review, we discuss steps involved in vertebrate mouth formation, using the frog Xenopus as a model. The vertebrate mouth derives from oral ectoderm from the anterior neural ridge, pharyngeal endoderm and cranial neural crest (NC). Vertebrates form a mouth by breaking through the body covering in a precise sequence including specification of EAD ectoderm and endoderm as well as NC, formation of a 'pre-mouth array,' basement membrane dissolution, stomodeum formation, and buccopharyngeal membrane perforation. In Xenopus, the EAD is also a craniofacial organizer that guides NC, while reciprocally, the NC signals to the EAD to elicit its morphogenesis into a pre-mouth array. Human mouth anomalies are prevalent and are affected by genetic and environmental factors, with understanding guided in part by use of animal models. WIREs Dev Biol 2017, 6:e275. doi: 10.1002/wdev.275 For further resources related to this article, please visit the WIREs website.

The rapid turnover of intestinal epithelial cells is maintained by a small number of stem cells located in pocket-like gland structures called crypts. While our understanding of the identity and function of intestinal stem cells (ISCs) has rapidly progressed, epigenetic and transcriptional regulation in crypt stem cell and progenitor pools remains an active field of investigation. Surrounded by various types of cells in the stroma, crypt progenitors display high levels of plasticity, harboring the ability to interconvert in the face of epithelial damage. Recent studies analyzing epigenetic patterns of intestinal epithelial cells have provided evidence that plasticity is maintained by a broadly permissive epigenomic state, wherein cell-lineage specification is directed through activation of signaling pathways and transcription factor (TF) expression. New studies also have shown that the ISC niche, which is comprised of surrounding epithelial and mesenchymal tissues, plays a crucial role in supporting the maintenance and differentiation of stem cells by providing contextual information in the form of signaling cascades, such as Wnt, Notch, and Hippo. These cascades ultimately govern TF expression to promote early cell-lineage decisions in both crypt stem cells and progenitors. Highlighting recent studies investigating signaling, transcriptional, and epigenetic mechanisms of intestinal epithelial cells, we will discuss the mechanisms underlying crypt homeostasis, plasticity, and niches. WIREs Dev Biol 2017, 6:e281. doi: 10.1002/wdev.281 For further resources related to this article, please visit the WIREs website.

Synaptic transmission is dynamic, plastic, and highly regulated. Drosophila is an advantageous model system for genetic and molecular studies of presynaptic and postsynaptic mechanisms and plasticity. Electrical recordings of synaptic responses represent a wide-spread approach to study neuronal signaling and synaptic transmission. We discuss experimental techniques that allow monitoring synaptic transmission in Drosophila neuromuscular and central systems. Recordings of synaptic potentials or currents at the larval neuromuscular junction (NMJ) are most common and provide numerous technical advantages due to robustness of the preparation, large and identifiable muscles, and synaptic boutons which can be readily visualized. In particular, focal macropatch recordings combined with the analysis of neurosecretory quanta enable rigorous quantification of the magnitude and kinetics of transmitter release. Patch-clamp recordings of synaptic transmission from the embryonic NMJ enable overcoming the problem of lethality in mutant lines. Recordings from the adult NMJ proved instrumental in the studies of temperature-sensitive paralytic mutants. Genetic studies of behavioral learning in Drosophila compel an investigation of synaptic transmission in the central nervous system (CNS), including primary cultured neurons and an intact brain. Cholinergic and GABAergic synaptic transmission has been recorded from the Drosophila CNS both in vitro and in vivo. In vivo patch-clamp recordings of synaptic transmission from the neurons in the olfactory pathway is a very powerful approach, which has a potential to elucidate how synaptic transmission is associated with behavioral learning. WIREs Dev Biol 2017, 6:e277. doi: 10.1002/wdev.277 For further resources related to this article, please visit the WIREs website.

The field of metabolic research has experienced an unexpected renaissance. While this renewed interest in metabolism largely originated in response to the global increase in diabetes and obesity, studies of metabolic regulation now represent the frontier of many biomedical fields. This trend is especially apparent in developmental biology, where metabolism influences processes ranging from stem cell differentiation and tissue growth to sexual maturation and reproduction. In this regard, the fruit fly Drosophila melanogaster has emerged as a powerful tool for dissecting conserved mechanisms that underlie developmental metabolism, often with a level of detail that is simply not possible in other animals. Here we describe why the fly is an ideal system for exploring the relationship between metabolism and development, and outline a basic experimental strategy for conducting these studies. WIREs Dev Biol 2017, 6:e280. doi: 10.1002/wdev.280 For further resources related to this article, please visit the WIREs website.

The measurement of cell proliferation in vivo is usually carried out by the examination of static measures. These comprise the mitotic index or labeling indices using incorporation of DNA synthesis markers such as bromodeoxyuridine or tritiated thymidine, or intrinsic markers, such as Ki67 and proliferative cell nuclear antigen (PCNA). But static measures only provide a 'snapshot' of cell proliferation. Rate measures, including double labeling methods and the metaphase arrest method, can actually measure cell production rates but they are far less utilized at present. Transit times and migration rates can also be measured using pulse and chase labeling or by following the transit of labeled cells through the tissue. Simple indices of cell division can easily be confounded by concomitant changes in the compartment size and many alleged markers of proliferation have serious shortcomings, as the markers may be involved in multiple aspects of cell regulation. The complexities of studying proliferation in vivo are illustrated here with a focus on the gastrointestinal tract. Some of these methods can help elucidate the role of the stem cells and their relationship to label retaining cells. WIREs Dev Biol 2017, 6:e274. doi: 10.1002/wdev.274 For further resources related to this article, please visit the WIREs website.

Functional annotation of mutations that cause human limb anomalies is enabled by basic developmental studies. In this study, we focus on the prepatterning stage of limb development and discuss a recent model that proposes anterior and posterior domains of the early limb bud generate two halves of the future skeleton. By comparing phenotypes in humans with those in model organisms, we evaluate whether this prepatterning concept helps to annotate human disease alleles. WIREs Dev Biol 2017, 6:e270. doi: 10.1002/wdev.270 For further resources related to this article, please visit the WIREs website.

A recent outbreak of Zika virus (ZIKV) in Brazil is associated with microcephaly in infants born of infected mothers. As this pandemic spreads, rapid scientific investigation is shedding new light on how prenatal infection with ZIKV causes microcephaly. In this analysis we provide an overview of both microcephaly and ZIKV, explore the connection between prenatal ZIKV infection and microcephaly, and highlight recent insights into how prenatal ZIKV infection depletes the pool of neural progenitors in the developing brain. WIREs Dev Biol 2017, 6:e273. doi: 10.1002/wdev.273 For further resources related to this article, please visit the WIREs website.

Tissue patterning during animal development is orchestrated by a handful of inductive signals. Most of these developmental cues act as morphogens, meaning they are locally produced secreted molecules that act at a distance to govern tissue patterning. The iterative use of the same signaling molecules in different developmental contexts demands that signal interpretation occurs in a highly context-dependent manner. Hence the interpretation of signal depends on the specific competence of the receiving cells. Moreover, it has become clear that the differential interpretation of morphogens depends not only on the level of signaling but also the signaling dynamics, particularly the duration of signaling. In this review, we outline molecular mechanisms proposed in recent studies that explain how the response to morphogens is determined by differential competence, pathway intrinsic feedback, and the interpretation of signaling dynamics by gene regulatory networks. WIREs Dev Biol 2017, 6:e271. doi: 10.1002/wdev.271 For further resources related to this article, please visit the WIREs website.