Regulatory Logic Underlying Diversification of the Neural Crest

Abstract

The neural crest is a transient, multipotent population of cells that arises at the border of the developing nervous system. After closure of the neural tube, these cells undergo an epithelial to mesenchymal transition to delaminate and migrate, often to distinct locations in the embryo. Neural crest cells give rise to a diverse array of derivatives including neurons and glia of the peripheral nervous system, melanocytes, and bone and cartilage of the face. A gene regulatory network (GRN) controls specification, delamination, migration, and differentiation of this fascinating cell type. With increasing technological advances, direct linkages within the neural crest GRN are being uncovered. The underlying circuitry is useful for understanding important topics such as reprogramming, evolution, and disease.

Specifying neural crest cells: From chromatin to morphogens and factors in between

“…Studies from multiple organisms (frog, chick, zebrafish, mouse and lamprey) have provided evidence for the existence of a putative pan-vertebrate NC GRN that describes the hierarchical interactions between signaling molecules and transcription factors during NC formation (Figure 6) (reviewed in Betancur, Bronner-Fraser, & Sauka-Spengler, 2010a; Martik & Bronner, 2017; Meulemans & Bronner-Fraser, 2005; Simoes-Costa & Bronner, 2015). Inductive signals (BMP, FGF, WNT, Notch, and their antagonists) from the NP, nonneural ectoderm, and underlying mesoderm interact to establish a broad region at the border of the NP by activating a battery of transcription factors (NPB specifiers).…”

Adult tissue–derived neural crest-like stem cells: Sources, regulatory networks, and translational potential

“…It is now clear that an intricate array of transcription factors and signaling molecules act in concert to imbue NC cells with its broad multipotency and migratory ability. These factors have been proposed to act via a multistep NC gene regulatory network (GRN) that integrates transcriptional inputs and diverse environmental signals . The NC GRN consists of a series of hierarchically arranged regulatory steps, including induction of the prospective NC at the neural plate border, specification of multipotent NC cells within the dorsal neural tube, control of their delamination via an epithelial to mesenchymal transition to produce a migratory population, and finally, diversification into distinct cell lineages.…”

“…Although NC stem cells are a transient cell population in developing embryos, multiple investigators have isolated cells with NC‐like characteristics, including transcriptional profile and differentiation potential, from a variety of adult tissues like DRG, bone marrow, skin, carotid body, whisker pad, heart, gut, and cranial tissues like cornea, iris, hard palate, dental pulp, and oral mucosa . Regardless of source, NC‐like cells have been coaxed to differentiate into SC, neurons, chondrocytes, smooth muscle cells, and even cardiomyocytes, providing a multipotent stem cell source for the treatment of demyelinating and other neurodegenerative disorders. Patient‐derived NCISCs harboring mutations for neurogenic diseases may also be used to study disease pathogenesis as well as provide a platform for drug screening further increasing their clinical potential …”

“…Often referred to as the “fourth germ layer,” the neural crest (NC) is a multipotent and migratory stem cell population that contributes to a wide array of organs and tissues in the vertebrate embryo, including autonomic ganglia, sensory neurons, adrenal and thyroid glands, cartilage and bone of the face, smooth muscle cells of some major arteries, and melanocytes in the skin . NC formation is first observed at stage 9 of human embryogenesis and extends till stage 20 as per the Carnegie staging system .…”

A snail tale and the chicken embryo

“…Experiments were carried out jointly in Spain, the UK and US, proving to be a truly fantastic example of collaborative work and publishing the results before I had even met Marianne in person. The chick embryo has continued to be a key model in the analysis of developmental processes (Stern, 2005;Gerety et al, 2013) and in particular, of the neural crest (Le Douarin and Dieterlen-Lièvre, 2013;Martik and Bronner, 2017, and references therein), for which Nicole and Marianne have played instrumental roles (see Fig. 2).…”