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Specification and Formation of the Neural Crest: Perspectives on Lineage Segregation

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Specification and Formation of the Neural Crest: Perspectives on Lineage Segregation Received: 3 November 2018 Revised: 17 December 2018 Accepted: 18 December 2018 DOI: 10.1002/dvg.23276 REVIEW Specification and formation of the neural crest: Perspectives on lineage segregation Maneeshi S. Prasad1 | Rebekah M. Charney1 | Martín I. García-Castro Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Summary California The neural crest is a fascinating embryonic population unique to vertebrates that is endowed Correspondence with remarkable differentiation capacity. Thought to originate from ectodermal tissue, neural Martín I. García-Castro, Division of Biomedical crest cells generate neurons and glia of the peripheral nervous system, and melanocytes Sciences, School of Medicine, University of California, Riverside, CA. throughout the body. However, the neural crest also generates many ectomesenchymal deriva- Email: [email protected] tives in the cranial region, including cell types considered to be of mesodermal origin such as Funding information cartilage, bone, and adipose tissue. These ectomesenchymal derivatives play a critical role in the National Institute of Dental and Craniofacial formation of the vertebrate head, and are thought to be a key attribute at the center of verte- Research, Grant/Award Numbers: brate evolution and diversity. Further, aberrant neural crest cell development and differentiation R01DE017914, F32DE027862 is the root cause of many human pathologies, including cancers, rare syndromes, and birth mal- formations. In this review, we discuss the current findings of neural crest cell ontogeny, and con- sider 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, craniofacial development, embryonic stem cells, epigenetic, FGF, gene regulatory network, induction, multipotent, neural crest cells, neural plate border, specification, Wnt 1 | INTRODUCTION aggressive cancers such as neuroblastoma and melanoma (Etchevers, Amiel, & Lyonnet, 2006; Farlie, McKeown, & Newgreen, 2004; Watt & The neural crest is an embryonic, multipotent cell population that Trainor, 2014). Of particular clinical relevance, craniofacial malforma- migrates extensively and gives rise to a multitude of derivatives tions account for over one-third of all congenital birth defects throughout the body, including melanocytes, peripheral neurons and (Twigg & Wilkie, 2015). Many distinct craniofacial syndromes exist, glia, and craniofacial bone, cartilage, and connective tissue. Neural including cleft lip and cleft palate (which occurs in 1:700 live births in crest cells are unique to vertebrates, and have defined the taxa by the United States [Leslie et al., 2015]), missing or improperly fused contributing to the evolution of key features of the predatory lifestyle, bones of the face and skull (including craniosynostosis), and mal- including a jaw, a larger brain enclosure, and paired sense organs formed teeth and facial features (Trainor, 2010; Twigg & Wilkie, (Gans & Northcutt, 1983; Northcutt, 2005). Owing to the broad con- 2015). Since their discovery 150 years ago (His, 1868), neural crest tribution of neural crest cells to derivatives throughout the body, a biology has captivated the interests of scientists, and the origins, for- large number of human health conditions are associated with mation, and differentiation capacity of neural crest cells, as well as improper neural crest development and differentiation. Collectively their associated pathologies, continue to be the subject of intense known as “neurocristopathies” (Bolande, 1974, 1997; Vega-Lopez, research. Cerrizuela, Tribulo, & Aybar, 2018), these include craniofacial malfor- Neural crest cells were first identified in chick embryos by Wil- mations, rare diseases such as Waardenburg syndrome, and helm His in 1868, who described them as a middle furrow or groove (“zwischenrinne”) surrounding the neural plate in early stages, and 1Maneeshi S. Prasad and Rebekah M. Charney contributed equally to this work. once the neural tube was formed, as a middle cord or thread genesis. 2019;57:e23276. wileyonlinelibrary.com/journal/dvg © 2018 Wiley Periodicals, Inc. 1 of 21 https://doi.org/10.1002/dvg.23276 2 of 21 PRASAD ET AL. (“zwischengstrang”) of tissue in-between the neural tube and the epi- perspective of a novel pre-border state during neural crest specifica- dermis (Dupont, 2018; Garcia-Castro, 2011; His, 1868). Neural crest tion prior to the formation of neural plate border state. cells develop along most of the embryonic anteroposterior axis and exhibit specific differentiation capacities according to their axial iden- 2 | EARLY STEPS IN NEURAL CREST tity. Therefore, neural crest cells are generally grouped as cranial FORMATION (cephalic), vagal, trunk, and sacral according to their position within the anteroposterior axis of the embryo. While neural crest from these Neural crest cell formation is a progressive process involving the com- locations have been shown to contribute to a specific set of deriva- binatorial interactions between signaling pathways and transcription tives, elegant heterotopic grafting experiments performed in birds factors (Figure 1). The neural crest is considered to be of ectodermal revealed the plasticity of pre-migratory neural crest cells, and the criti- origin, arising between the developing neural plate and the nonneural cal role of the unique environment surrounding migratory neural crest ectoderm, in a region termed as the neural plate border. There is con- in differentiation (Le Douarin, 1980; Le Douarin, Creuzet, Couly, & siderable evidence supporting the role of inductive processes in neural Dupin, 2004; Noden, 1975, 1988; Rothstein, Bhattacharya, & Simões- crest formation, and signaling pathways including Wnt, BMP, FGF and Costa, 2018). Notch from neural and nonneural ectoderm, and mesoderm tissues Neural crest cell development and migration occurs in a rostro- have all been implicated (reviewed in Stuhlmiller & García-Castro, caudal wave with the neural crest from the cranial region being the 2012a). However, this model has perplexed biologists when viewed in first to undergo an epithelial-to-mesenchymal transition (EMT). Cra- light of concepts of cell fate restrictions. As neural crest cells hold the nial neural crest cells migrate along a well-defined dorsolateral path- capacity to differentiate into cells types commonly assumed to be way, where they populate defined regions of the embryo and derived from ectoderm and mesoderm germ layers, it would seem that differentiate to give rise to much of the craniofacial skeleton, para- their potential is even greater than the cells from which they are pro- sympathetic and sensory ganglia, and endocrine and pigment cells. At posed to originate. While the fields of somatic cell reprogramming and more caudal axial levels, trunk neural crest cells arise from the dorsal stem cell biology have revealed the tremendous capacity of cells to aspect of the neural tube and contribute to derivatives that include dedifferentiate and acquire new fates (Gurdon, 1962; Gurdon, the peripheral neurons and glia, adrenomedullary cells, and pigment Byrne, & Simonsson, 2003; Jaenisch & Young, 2008), the principle of cells (Schlosser, 2008). Among the subpopulations of neural crest, it is sequential segregation of potential during normal embryonic develop- conventionally thought that only cranial neural crest could form ecto- ment is still well-regarded. Under this principle, progenitor cells gener- mesenchyme in amniotes, while anamniote trunk neural crest was ate derivatives with more restricted potential, and no other cell type capable of producing mesenchyme, in particular in the larval fin. How- apart from the neural crest has been suggested to bypass this princi- ever, recent studies have challenged these notions. Using genetic- ple. In this section, we discuss the evidence of the role of an induction based lineage tracing in zebrafish, it was observed that the larval fin mechanism in the formation of the neural crest, with details on the mesenchyme, originally thought to originate at least in part from the particular pathway components presented in the next section. We neural crest, is derived from the paraxial mesoderm (Lee, Knapik, Thi- then discuss recent work that brings to the forefront new questions ery, & Carney, 2013). Around the same time, lineage tracing in turtles of the origins and earliest specification events of neural crest. revealed a second wave of migratory trunk neural crest cells that con- tribute to the plastron bones (Cebra-Thomas et al., 2013). These 2.1 | Tissue interactions and neural crest induction intriguing results suggest that anamniote trunk neural crest does not contribute to mesenchymal derivatives, while amniote trunk neural The initial description by His, later confirmed by a wealth of studies in crest cells contributed to an ectomesenchymal derivate to some multiple organisms, located the neural crest and its precursors at the extent. These findings raise intriguing questions of neural crest plas- neural plate border, in-between the thicker medial neural plate and ticity and lineage restrictions that remain to be addressed. the thinner lateral nonneural ectoderm. Underneath these ectodermal Owing to the major contributions of the neural crest to the verte- cells, and in direct contact with them, a mesodermal layer is posi- brate body plan and related neurocristopathies,
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