A Spatio-Temporal-Dependent Requirement of Sonic Hedgehog in the Early Development of Sclerotome-Derived Vertebrae and Ribs.

Derived from axial structures, Sonic Hedgehog (Shh) is secreted into the paraxial mesoderm, where it plays crucial roles in sclerotome induction and myotome differentiation. Through conditional loss-of-function in quail embryos, we investigate the timing and impact of Shh activity during early formation of sclerotome-derived vertebrae and ribs, and of lateral mesoderm-derived sternum. To this end, Hedgehog interacting protein (Hhip) was electroporated at various times between days 2 and 5.

From neural tube to spinal cord: The dynamic journey of the dorsal neuroepithelium.

In a developing embryo, formation of tissues and organs is remarkably precise in both time and space. Through cell-cell interactions, neighboring progenitors coordinate their activities, sequentially generating distinct types of cells. At present, we only have limited knowledge, rather than a systematic understanding, of the underlying logic and mechanisms responsible for cell fate transitions.

Recent advances in understanding cell type transitions during dorsal neural tube development.

The vertebrate neural tube is a representative example of a morphogen-patterned tissue that generates different cell types with spatial and temporal precision. More specifically, the development of the dorsal region of the neural tube is of particular interest because of its highly dynamic behavior. First, early premigratory neural crest progenitors undergo an epithelial-to-mesenchymal transition, exit the neural primordium, and generate, among many derivatives, most of the peripheral nervous system.

Completion of neural crest cell production and emigration is regulated by retinoic-acid-dependent inhibition of BMP signaling.

Production and emigration of neural crest cells is a transient process followed by the emergence of the definitive roof plate. The mechanisms regulating the end of neural crest ontogeny are poorly understood. Whereas early crest development is stimulated by mesoderm-derived retinoic acid, we report that the end of the neural crest period is regulated by retinoic acid synthesized in the dorsal neural tube.

From Bipotent Neuromesodermal Progenitors to Neural-Mesodermal Interactions during Embryonic Development.

To ensure the formation of a properly patterned embryo, multiple processes must operate harmoniously at sequential phases of development. This is implemented by mutual interactions between cells and tissues that together regulate the segregation and specification of cells, their growth and morphogenesis. The formation of the spinal cord and paraxial mesoderm derivatives exquisitely illustrate these processes.

From Neural Crest to Definitive Roof Plate: The Dynamic Behavior of the Dorsal Neural Tube.

Research on the development of the dorsal neural tube is particularly challenging. In this highly dynamic domain, a temporal transition occurs between early neural crest progenitors that undergo an epithelial-to-mesenchymal transition and exit the neural primordium, and the subsequent roof plate, a resident epithelial group of cells that constitutes the dorsal midline of the central nervous system. Among other functions, the roof plate behaves as an organizing center for the generation of dorsal interneurons.

Notch signaling is a critical initiator of roof plate formation as revealed by the use of RNA profiling of the dorsal neural tube.

Background: The dorsal domain of the neural tube is an excellent model to investigate the generation of complexity during embryonic development. It is a highly dynamic and multifaceted region being first transiently populated by prospective neural crest (NC) cells that sequentially emigrate to generate most of the peripheral nervous system. Subsequently, it becomes the definitive roof plate (RP) of the central nervous system.

Neural tube development depends on notochord-derived sonic hedgehog released into the sclerotome.

Sonic hedgehog (Shh), produced in the notochord and floor plate, is necessary for both neural and mesodermal development. To reach the myotome, Shh has to traverse the sclerotome and a reduction of sclerotomal Shh affects myotome differentiation. By investigating loss and gain of Shh function, and floor-plate deletions, we report that sclerotomal Shh is also necessary for neural tube development.

Guidelines and definitions for research on epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) encompasses dynamic changes in cellular organization from epithelial to mesenchymal phenotypes, which leads to functional changes in cell migration and invasion. EMT occurs in a diverse range of physiological and pathological conditions and is driven by a conserved set of inducing signals, transcriptional regulators and downstream effectors. With over 5,700 publications indexed by Web of Science in 2019 alone, research on EMT is expanding rapidly.

YAP promotes neural crest emigration through interactions with BMP and Wnt activities.

Background: Premigratory neural crest progenitors undergo an epithelial-to-mesenchymal transition and leave the neural tube as motile cells. Previously, we showed that BMP generates trunk neural crest emigration through canonical Wnt signaling which in turn stimulates G1/S transition. The molecular network underlying this process is, however, not yet completely deciphered.

The Neural Crest: A Remarkable Model System for Studying Development and Disease.

Neural crest cells are the embryonic precursors of most neurons and all glia of the peripheral nervous system, pigment cells, some endocrine components, and connective tissue of the head, face, neck, and heart. Following induction, crest cells undergo an epithelial to mesenchymal transition that enables them to migrate along specific pathways culminating in their phenotypic differentiation. Researching this unique embryonic population has revealed important understandings of basic biological and developmental principles.

Neural crest emigration: From start to stop.

Within the dynamic context of a developing embryo, the multicellular patterns formed are extraordinarily precise. Through cell-cell communication, neighboring progenitors coordinate their activities, sequentially generating distinct tissues. The development of the dorsal neural tube remarkably illustrates this principle.

Cell fate decisions during neural crest ontogeny.

The neural crest (NC) originates in the central nervous system (CNS) primordium. Born as an epithelium, NC progenitors undergo an epithelial-to-mesenchymal transition that generates cellular movement away from the CNS. Mesenchymal NC progenitors then migrate through stereotypic pathways characteristic of various axial levels until homing to distinct primordia where phenotypic differentiation takes place.

Dynamics of BMP and Hes1/Hairy1 signaling in the dorsal neural tube underlies the transition from neural crest to definitive roof plate.

Background: The dorsal midline region of the neural tube that results from closure of the neural folds is generally termed the roof plate (RP). However, this domain is highly dynamic and complex, and is first transiently inhabited by prospective neural crest (NC) cells that sequentially emigrate from the neuroepithelium. It only later becomes the definitive RP, the dorsal midline cells of the spinal cord.

Epithelial-Mesenchymal Transitions during Neural Crest and Somite Development.

Epithelial-to-mesenchymal transition (EMT) is a central process during embryonic development that affects selected progenitor cells of all three germ layers. In addition to driving the onset of cellular migrations and subsequent tissue morphogenesis, the dynamic conversions of epithelium into mesenchyme and vice-versa are intimately associated with the segregation of homogeneous precursors into distinct fates. The neural crest and somites, progenitors of the peripheral nervous system and of skeletal tissues, respectively, beautifully illustrate the significance of EMT to the above processes.

A Novel Role for VICKZ Proteins in Maintaining Epithelial Integrity during Embryogenesis.

Background: VICKZ (IGF2BP1,2,3/ZBP1/Vg1RBP/IMP1,2,3) proteins bind RNA and help regulate many RNA-mediated processes. In the midbrain region of early chick embryos, VICKZ is expressed in the neural folds and along the basal surface of the neural epithelium, but, upon neural tube closure, is down-regulated in prospective cranial neural crest (CNC) cells, concomitant with their emigration and epithelial-to-mesenchymal transition (EMT). Electroporation of constructs that modulate cVICKZ expression demonstrates that this down-regulation is both necessary and sufficient for CNC EMT.

Neural-mesodermal progenitor interactions in pattern formation: an introduction to the collection.

Mesodermal and spinal cord progenitors originate from common founder cells from which they segregate during development. Moreover, neural and mesodermal tissues closely interact during embryogenesis to ensure timely patterning and differentiation of both head and trunk structures. For instance, the fate and morphogenesis of neural progenitors is dependent on signals produced by mesodermal cells and vice-versa.

Mechanisms of myogenic specification and patterning.

Mesodermal somites are initially composed of columnar cells arranged as a pseudostratified epithelium that undergoes sequential and spatially restricted changes to generate the sclerotome and dermomyotome, intermediate structures that develop into vertebrae, striated muscles of the body and limbs, dermis, smooth muscle, and endothelial cells. Regional cues were elucidated that impart differential traits upon the originally multipotent progenitors. How do somite cells and their intermediate progenitors interpret these extrinsic cues and translate them into various levels and/or modalities of intracellular signaling that lead to differential gene expression profiles remains a significant challenge.

Segregation of striated and smooth muscle lineages by a Notch-dependent regulatory network.

Background: Lineage segregation from multipotent epithelia is a central theme in development and in adult stem cell plasticity. Previously, we demonstrated that striated and smooth muscle cells share a common progenitor within their epithelium of origin, the lateral domain of the somite-derived dermomyotome. However, what controls the segregation of these muscle subtypes remains unknown.

Neural crest and Schwann cell progenitor-derived melanocytes are two spatially segregated populations similarly regulated by Foxd3.

Skin melanocytes arise from two sources: either directly from neural crest progenitors or indirectly from neural crest-derived Schwann cell precursors after colonization of peripheral nerves. The relationship between these two melanocyte populations and the factors controlling their specification remains poorly understood. Direct lineage tracing reveals that neural crest and Schwann cell progenitor-derived melanocytes are differentially restricted to the epaxial and hypaxial body domains, respectively.

Sympathetic neurons and chromaffin cells share a common progenitor in the neural crest in vivo.

Background: The neural crest (NC) is a transient embryonic structure unique to vertebrates, which generates peripheral sensory and autonomic neurons, glia, neuroendocrine chromaffin and thyroid C-cells, melanocytes, and mesenchymal derivatives such as parts of the skull, heart, and meninges. The sympathoadrenal (SA) cell lineage is one major sub-lineage of the NC that gives rise to sympathetic neurons, chromaffin cells, and the intermediate small intensely fluorescent (SIF) cells. A key question is when during NC ontogeny do multipotent progenitors segregate into the different NC-derived lineages.

A dynamic code of dorsal neural tube genes regulates the segregation between neurogenic and melanogenic neural crest cells.

Understanding when and how multipotent progenitors segregate into diverse fates is a key question during embryonic development. The neural crest (NC) is an exemplary model system with which to investigate the dynamics of progenitor cell specification, as it generates a multitude of derivatives. Based on 'in ovo' lineage analysis, we previously suggested an early fate restriction of premigratory trunk NC to generate neural versus melanogenic fates, yet the timing of fate segregation and the underlying mechanisms remained unknown.