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Specification and formation of the neural crest: Perspectives on lineage segregation - PubMed

Review

Specification and formation of the neural crest: Perspectives on lineage segregation

Maneeshi S Prasad et al. Genesis. 2019 Jan.

Abstract

The neural crest is a fascinating embryonic population unique to vertebrates that is endowed with remarkable differentiation capacity. Thought to originate from ectodermal tissue, neural crest cells generate neurons and glia of the peripheral nervous system, and melanocytes throughout the body. However, the neural crest also generates many ectomesenchymal derivatives in the cranial region, including cell types considered to be of mesodermal origin such as cartilage, bone, and adipose tissue. These ectomesenchymal derivatives play a critical role in the formation of the vertebrate head, and are thought to be a key attribute at the center of vertebrate evolution and diversity. Further, aberrant neural crest cell development and differentiation is the root cause of many human pathologies, including cancers, rare syndromes, and birth malformations. In this review, we discuss the current findings of neural crest cell ontogeny, and consider tissue, cell, and molecular contributions toward neural crest formation. We further provide current perspectives into the molecular network involved during the segregation of the neural crest lineage.

Keywords: BMP; FGF; Wnt; craniofacial development; embryonic stem cells; epigenetic; gene regulatory network; induction; multipotent; neural crest cells; neural plate border; specification.

© 2018 Wiley Periodicals, Inc.

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Figures

FIGURE 1
FIGURE 1

Dynamics of signaling molecules and transcription factors regulating neural crest cell induction from blastula to neurula stage. Neural crest formation is viewed as a progressive inductive process initiating at blastula stage and continuing through gastrulation into neurula stage. This process is mediated by Wnt, FGF, and BMP signaling cues and transduced by transcription factors. Experimental data from works cited in this review were used to provide a temporal perspective of signaling and transcription factor modules involved during different phases of neural crest induction. Under the signaling module, dotted lines represent the potential role of these signaling molecules during blastula stages where their requirement is unknown. Based on expression patterns, BMP/Smad1/5/8 signaling is active at blastula stage (Faure, de Santa Barbara, Roberts, & Whitman, 2002) as well as Wnt and FGF/Erk1/2 signaling. During NC development, Wnt signaling is known to play a role during gastrula and neurula stages, FGF/Erk1/2 signaling during gastrula stage, and BMP/Smad1/5/8 signaling during neurula stage (denoted by solid lines), however, their role during pre-gastrula stage remains to be analyzed. FGF/Erk1/2 signaling is active during neurula stage; however, it is not suggested to be involved in NC development at this stage (grey line). BMP/Smad1/5/8 signaling is active during gastrula stage, but needs to be attenuated in cells specified towards NC fate, represented by the gap in the blue BMP signaling line. The transcription factor module provides a hierarchical view of the requirement of specific transcription factors during the different phases of neural crest induction. The transcription factors mentioned under blastula stage were identified from studies in a human neural crest model based on embryonic stem cells. The network of transcription factors involved in neural crest specification at blastula stage in animal models remains to be identified. NC = neural crest; NNE = nonneural ectoderm; NP = neural plate; pNC = prospective neural crest; pNP = prospective neural plate, PPE = preplacodal ectoderm). Schematics of gastrula and neurula chick embryos are adapted from Stuhlmiller & GarcííaCastro, 2012a

FIGURE 2
FIGURE 2

Gene regulatory network governing the specification and formation of neural crest cells. Proposed gene regulatory network involved in neural crest induction based on available literature. The recently proposed pre-border state based on the human neural crest model system depicts potential signaling pathways that may be involved at this stage according to their known expression patterns in different species. The transcription factors at this stage were identified from studies in human neural crest specification. The neural plate border (NPB) and subsequent neural crest (pre-migratory) states follow the pre-border state, and depict an updated version of the neural crest gene regulatory network compiled from studies in chick, mouse, human, Xenopus, and zebrafish model systems. The GRN model was built using BioTapestry software (Longabaugh et al., 2009)

FIGURE 3
FIGURE 3

Stem cell-based model of human neural crest development. Schematic depicting the neural crest differentiation protocol using human embryonic stem cells (hES) or human induced pluripotent stem cells (hiPS) as described in Leung et al. (2016). The neural crest induction from hES/hiPS cells begins with the activation of Wnt signaling using the GSK3 inhibitor CHIR99021, and neural crest cell formation is complete on Day 5. Different phases of neural crest development, including pre-border, neural plate border (NPB) and neural crest state, have been designated based on the in vivo expression of known neural crest markers during 5 days of induction. The large amounts of synchronous neural crest cells obtained at Day 5 can be used to obtain all known neural crest derivatives (Leung et al., 2016) to address neural crest pathologies

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