Specification of the neural plate border

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Homo sapiens
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The neural plate border forms on the dorsal side of the embryo between the medial neural plate and the lateral epidermis. This region has intermediate BMP and FGF signaling, with WNT also playing a role in specification (reviewed in Patthey and Gunhaga 2011, Simoes-Costa and Bronner 2015, Thawani and Groves 2020). Within the neural plate border, FGF signaling appears to repress formation of epidermis while BMP appears to repress formation of neural cells (reviewed in Patthey and Gunhaga 2014). During neural plate border specification, the most anterior part is a WNT-free domain and the posterior part is exposed to WNT activity (reviewed in Patthey and Gunhaga 2011, Patthey and Gunhaga 2014).
As the neural plate folds to form the neural tube, the neural plate border contributes to the olfactory, lens, and hypophyseal placodes in the anterior region and the neural crest in the posterior region (reviewed in Singh and Groves 2016, Koontz et al. 2023). In addition, the otic placodes and cranial sensory placodes arise immediately lateral to the neural crest. The neural crest is a population of migratory cells located dorsal to the neural tube that is unique to vertebrates (reviewed in Cheung et al. 2019) and gives rise to several cell types, including neurons and glia of the peripheral nervous system, osteoblasts and chondrocytes of the craniofacial skeleton, adrenal medulla cells, and melanocytes (reviewed in Kalcheim and Kumar 2017). Placodes generate the olfactory epithelium, the lens of the eye, the inner ear, the endocrine adenohypophysis of the pituitary gland, and some neurons of the cranial sensory ganglia (reviewed in Alsina 2020).
The neural plate border is specified by a combination of transcription factors including GBX2, TFAP2A, MSX1, MSX2, ZIC1, ZIC3, DLX5/6, PAX3, and PAX7. These factors may also be expressed in additional, overlapping regions. For example ZIC1 is expressed in the neural plate border and more medially in the neural plate, where it is involved in neural induction. TFAP2A is expressed in the neural plate border and more laterally in the epidermis. Thus the neural plate border is defined by a combination of factors rather than by a single factor (reviewed in Prasad et al. 2019).
The order of expression of neural plate border specifiers is not completely characterized in humans. In human embryonic stem cells differentiated in vitro, GBX2 is expressed broadly in the posterior ectoderm, then TFAP2A, PAX3, PAX7, and MSX1 are expressed in a neural plate border state (Leung et al. 2016). The primacy of Gbx2 is also observed in Xenopus embryos (Li et al. 2009). These genes then cross-regulate each other's expression to create a self-reinforcing module.
Literature References
PubMed ID Title Journal Year
26839343 WNT/β-catenin signaling mediates human neural crest induction via a pre-neural border intermediate

Prasad, MS, Murdoch, B, Gomez, GA, Salem, AF, García-Castro, MI, Leung, AW

Development 2016
32950922 Mechanisms of cell specification and differentiation in vertebrate cranial sensory systems

Alsina, B

Curr Opin Cell Biol 2020
26952139 The molecular basis of craniofacial placode development

Singh, S, Groves, AK

Wiley Interdiscip Rev Dev Biol 2016
35787974 On the evolutionary origins and regionalization of the neural crest

Simoes-Costa, M, Rothstein, M

Semin Cell Dev Biol 2023
35760729 Making a head: Neural crest and ectodermal placodes in cranial sensory development

Bronner, ME, Urrutia, HA, Koontz, A

Semin Cell Dev Biol 2023
25903629 Evolution of vertebrates as viewed from the crest

Bronner, ME, Simoes-Costa, M, Green, SA

Nature 2015
28621417 Cell fate decisions during neural crest ontogeny

Kalcheim, C, Kumar, D

Int J Dev Biol 2017
33364980 Building the Border: Development of the Chordate Neural Plate Border Region and Its Derivatives

Thawani, A, Groves, AK

Front Physiol 2020
19736322 The posteriorizing gene Gbx2 is a direct target of Wnt signalling and the earliest factor in neural crest induction

Moreno, M, Mayor, R, Kuriyama, S, Li, B

Development 2009
31470291 Acquisition of multipotent and migratory neural crest cells in vertebrate evolution

Lu, PJ, Cheung, M, Cheah, KS, Tai, A

Curr Opin Genet Dev 2019
22103410 Specification and regionalisation of the neural plate border

Patthey, C, Gunhaga, L

Eur J Neurosci 2011
29852131 The neural border: Induction, specification and maturation of the territory that generates neural crest cells

Pla, P, Monsoro-Burq, AH

Dev Biol 2018
30576078 Specification and formation of the neural crest: Perspectives on lineage segregation

Prasad, MS, Charney, RM, García-Castro, MI

Genesis 2019
23939346 Signaling pathways regulating ectodermal cell fate choices

Patthey, C, Gunhaga, L

Exp Cell Res 2014
25564621 Establishing neural crest identity: a gene regulatory recipe

Bronner, ME, Simoes-Costa, M

Development 2015
28352644 Signaling pathways and tissue interactions in neural plate border formation

Schambony, A, Schille, C

Neurogenesis (Austin) 2017
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