Wiley Interdisciplinary Reviews: Developmental Biology最新文献

Many animal species are capable of replacing missing tissues that are lost upon injury or amputation through the process of regeneration. Although the extent of regeneration is variable across animals, that is, some animals can regenerate any missing cell type whereas some can only regenerate certain organs or tissues, regulated cell proliferation underlies the formation of new tissues in most systems. Notably, many species display an increase in proliferation within hours or days upon wounding. While different cell types proliferate in response to wounding in various animal taxa, comparative molecular data are beginning to point to shared wound-induced mechanisms that regulate cell division during regeneration. Here, we synthesize current insights about early molecular pathways of regeneration from diverse model and emerging systems by considering these species in their evolutionary contexts. Despite the great diversity of mechanisms underlying injury-induced cell proliferation across animals, and sometimes even in the same species, similar pathways for proliferation have been implicated in distantly related species (e.g., small diffusible molecules, signaling from apoptotic cells, growth factor signaling, mTOR and Hippo signaling, and Wnt and Bmp pathways). Studies that explicitly interrogate molecular and cellular regenerative mechanisms in understudied animal phyla will reveal the extent to which early pathways in the process of regeneration are conserved or independently evolved. This article is categorized under: Comparative Development and Evolution > Body Plan Evolution Adult Stem Cells, Tissue Renewal, and Regeneration > Regeneration Comparative Development and Evolution > Model Systems.

Cell type-specific transcription is a key determinant of cell fate and function. An ongoing challenge in biology is to develop robust and stringent biochemical methods to explore gene expression with cell type specificity. This challenge has become even greater as researchers attempt to apply high-throughput RNA analysis methods under in vivo conditions. TU-tagging and EC-tagging are in vivo biosynthetic RNA tagging techniques that allow spatial and temporal specificity in RNA purification. Spatial specificity is achieved through targeted expression of pyrimidine salvage enzymes (uracil phosphoribosyltransferase and cytosine deaminase) and temporal specificity is achieved by controlling exposure to bioorthogonal substrates of these enzymes (4-thiouracil and 5-ethynylcytosine). Tagged RNAs can be purified from total RNA extracted from an animal or tissue and used in transcriptome profiling analyses. In addition to identifying cell type-specific mRNA profiles, these techniques are applicable to noncoding RNAs and can be used to measure RNA transcription and decay. Potential applications of TU-tagging and EC-tagging also include fluorescent RNA imaging and selective definition of RNA-protein interactions. TU-tagging and EC-tagging hold great promise for supporting research at the intersection of RNA biology and developmental biology. This article is categorized under: Technologies > Analysis of the Transcriptome.

The phylogenetic position of echinoderms is well suited to revealing shared features of deuterostomes that distinguish them from other bilaterians. Although echinoderm neurobiology remains understudied, genomic resources, molecular methods, and systems approaches have enabled progress in understanding mechanisms of embryonic neurogenesis. Even though the morphology of echinoderm larvae is diverse, larval nervous systems, which arise during gastrulation, have numerous similarities in their organization. Diverse neural subtypes and specialized sensory neurons have been identified and details of neuroanatomy using neuron-specific labels provide hypotheses for neural function. The early patterning of ectoderm and specification of axes has been well studied in several species and underlying gene regulatory networks have been established. The cells giving rise to central and peripheral neural components have been identified in urchins and sea stars. Neurogenesis includes typical metazoan features of asymmetric division of neural progenitors and in some cases limited proliferation of neural precursors. Delta/Notch signaling has been identified as having critical roles in regulating neural patterning and differentiation. Several transcription factors functioning in pro-neural phases of specification, neural differentiation, and sub-type specification have been identified and structural or functional components of neurons are used as differentiation markers. Several methods for altering expression in embryos have revealed aspects of a regulatory hierarchy of transcription factors in neurogenesis. Interfacing neurogenic gene regulatory networks to the networks regulating ectodermal domains and identifying the spatial and temporal inputs that pattern the larval nervous system is a major challenge that will contribute substantially to our understanding of the evolution of metazoan nervous systems. This article is categorized under: Comparative Development and Evolution > Model Systems Comparative Development and Evolution > Body Plan Evolution Early Embryonic Development > Gastrulation and Neurulation.

Understanding how individual cells make fate decisions that lead to the faithful formation and homeostatic maintenance of tissues is a fundamental goal of contemporary developmental and stem cell biology. Seemingly uniform populations of stem cells and multipotent progenitors display a surprising degree of heterogeneity, primarily originating from the inherent stochastic nature of molecular processes underlying gene expression. Despite this heterogeneity, lineage decisions result in tissues of a defined size and with consistent proportions of differentiated cell types. Using the early mouse embryo as a model we review recent developments that have allowed the quantification of molecular intercellular heterogeneity during cell differentiation. We first discuss the relationship between these heterogeneities and developmental cellular potential. We then review recent theoretical approaches that formalize the mechanisms underlying fate decisions in the inner cell mass of the blastocyst stage embryo. These models build on our extensive knowledge of the genetic control of fate decisions in this system and will become essential tools for a rigorous understanding of the connection between noisy molecular processes and reproducible outcomes at the multicellular level. We conclude by suggesting that cell-to-cell communication provides a mechanism to exploit and buffer intercellular variability in a self-organized process that culminates in the reproducible formation of the mature mammalian blastocyst stage embryo that is ready for implantation into the maternal uterus. This article is categorized under: Gene Expression and Transcriptional Hierarchies > Cellular Differentiation Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics Gene Expression and Transcriptional Hierarchies > Quantitative Methods and Models.

The convergence of developmental biology and modern genomics tools brings the potential for a comprehensive understanding of developmental systems. This is especially true for the Caenorhabditis elegans embryo because its small size, invariant developmental lineage, and powerful genetic and genomic tools provide the prospect of a cellular resolution understanding of messenger RNA (mRNA) expression and regulation across the organism. We describe here how a systems biology framework might allow large-scale determination of the embryonic regulatory relationships encoded in the C. elegans genome. This framework consists of two broad steps: (a) defining the "parts list"-all genes expressed in all cells at each time during development and (b) iterative steps of computational modeling and refinement of these models by experimental perturbation. Substantial progress has been made towards defining the parts list through imaging methods such as large-scale green fluorescent protein (GFP) reporter analysis. Imaging results are now being augmented by high-resolution transcriptome methods such as single-cell RNA sequencing, and it is likely the complete expression patterns of all genes across the embryo will be known within the next few years. In contrast, the modeling and perturbation experiments performed so far have focused largely on individual cell types or genes, and improved methods will be needed to expand them to the full genome and organism. This emerging comprehensive map of embryonic expression and regulatory function will provide a powerful resource for developmental biologists, and would also allow scientists to ask questions not accessible without a comprehensive picture. This article is categorized under: Invertebrate Organogenesis > Worms Technologies > Analysis of the Transcriptome Gene Expression and Transcriptional Hierarchies > Gene Networks and Genomics.

Hematopoiesis is a complex process with a variety of different signaling pathways influencing every step of blood cell formation from the earliest precursors to final differentiated blood cell types. Formation of blood cells is crucial for survival. Blood cells carry oxygen, promote organ development and protect organs in different pathological conditions. Hematopoietic stem and progenitor cells (HSPCs) are responsible for generating all adult differentiated blood cells. Defects in HSPCs or their downstream lineages can lead to anemia and other hematological disorders including leukemia. The zebrafish has recently emerged as a powerful vertebrate model system to study hematopoiesis. The developmental processes and molecular mechanisms involved in zebrafish hematopoiesis are conserved with higher vertebrates, and the genetic and experimental accessibility of the fish and the optical transparency of its embryos and larvae make it ideal for in vivo analysis of hematopoietic development. Defects in zebrafish hematopoiesis reliably phenocopy human blood disorders, making it a highly attractive model system to screen small molecules to design therapeutic strategies. In this review, we summarize the key developmental processes and molecular mechanisms of zebrafish hematopoiesis. We also discuss recent findings highlighting the strengths of zebrafish as a model system for drug discovery against hematopoietic disorders. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Stem Cell Differentiation and Reversion Vertebrate Organogenesis > Musculoskeletal and Vascular Nervous System Development > Vertebrates: Regional Development Comparative Development and Evolution > Organ System Comparisons Between Species.

Molluscan shells are externally fabricated by specialized epithelial cells on the dorsal mantle. Although a conserved set of regulatory genes appears to underlie specification of mantle progenitor cells, the genes that contribute to the formation of the mature shell are incredibly diverse. Recent comparative analyses of mantle transcriptomes and shell proteomes of gastropods and bivalves are consistent with shell diversity being underpinned by a rapidly evolving mantle secretome (suite of genes expressed in the mantle that encode secreted proteins) that is the product of (a) high rates of gene co-option into and loss from the mantle gene regulatory network, and (b) the rapid evolution of coding sequences, particular those encoding repetitive low complexity domains. Outside a few conserved genes, such as carbonic anhydrase, a so-called "biomineralization toolkit" has yet to be discovered. Despite this, a common suite of protein domains, which are often associated with the extracellular matrix and immunity, appear to have been independently and often uniquely co-opted into the mantle secretomes of different species. The evolvability of the mantle secretome provides a molecular explanation for the evolution and diversity of molluscan shells. These genomic processes are likely to underlie the evolution of other animal biominerals, including coral and echinoderm skeletons. This article is categorized under: Comparative Development and Evolution > Regulation of Organ Diversity Comparative Development and Evolution > Evolutionary Novelties.

The Müllerian ducts are part of the embryonic urogenital system. They give rise to mature structures that serve a critical function in the transport and development of the oocyte and/or embryo. In most vertebrates, both sexes initially develop Müllerian ducts during embryogenesis, but they regress in males under the influence of testis-derived Anti-Müllerian Hormone (AMH). A number of regulatory factors have been shown to be essential for proper duct development, including Bmp and Wnt signaling molecules, together with homeodomain transcription factors such as PAX2 and LIM1. Later in development, the fate of the ducts diverges between males and females and is regulated by AMH and Wnt signaling molecules (duct regression in males) and Hox genes (duct patterning in females). Most of the genes and molecular pathways known to be involved in Müllerian duct development have been elucidated through animal models, namely, the mouse and chicken. In addition, genetic analysis of humans with reproductive tract disorders has further defined molecular mechanisms of duct formation and differentiation. However, despite our current understanding of Müllerian duct development, some questions remain to be answered at the molecular genetic level. This article is categorized under: Early Embryonic Development > Development to the Basic Body Plan.