Building the Border: Development of the Chordate Neural Plate Border Region and Its Derivatives

Abstract

The paired cranial sensory organs and peripheral nervous system of vertebrates arise from a thin strip of cells immediately adjacent to the developing neural plate. The neural plate border region comprises progenitors for four key populations of cells: neural plate cells, neural crest cells, the cranial placodes, and epidermis. Putative homologues of these neural plate border derivatives can be found in protochordates such as amphioxus and tunicates. In this review, we summarize key signaling pathways and transcription factors that regulate the inductive and patterning events at the neural plate border region that give rise to the neural crest and placodal lineages. Gene regulatory networks driven by signals from WNT, fibroblast growth factor (FGF), and bone morphogenetic protein (BMP) signaling primarily dictate the formation of the crest and placodal lineages. We review these studies and discuss the potential of recent advances in spatio-temporal transcriptomic and epigenomic analyses that would allow a mechanistic understanding of how these signaling pathways and their downstream transcriptional cascades regulate the formation of the neural plate border region.

Repressive Interactions Between Transcription Factors Separate Different Embryonic Ectodermal Domains

“…Many previous studies showed that as the embryonic ectoderm gradually resolves into four distinct domains, numerous TFs are expressed in overlapping patterns that eventually segregate during neurulation into NP, NC, PPR and Epi, each of which characteristically expresses a subset of these TFs (reviewed in Moody and LaMantia, 2015;Seal and Monsoro-Burq, 2020;Thawani and Groves, 2020;Schlosser 2021). It is commonly posed that the overlapping expression domains are sharpened into distinct domains by repressive interactions between these TFs, similar to the interactions between gap genes during segmentation in Drosophila (reviewed in Jaeger, 2011).…”

“…It is well appreciated that the embryonic ectoderm becomes separated into neural and non-neural domains in response to signaling gradients of various growth factors, in particular BMP, Wnt and FGF (reviewed in Stuhlmiller and Garcia-Castro, 2012;Saint-Jeannet and Moody, 2014;Pla and Monsoro-Burq, 2018;Streit, 2018;Schlosser, 2021). By the time that the neural tube closes four domains -NP, NC, PPR and Epi-can be distinguished by a distinct suite of TFs that are thought to impose domain-specific identity (reviewed in Milet and Monsoro-Burq, 2012;Moody and LaMantia, 2015;Streit, 2018;Seal and Monsoro-Burq, 2020;Thawani and Groves, 2020). However, a number of studies have shown that the TFs that we used in our study as landmarks of these four domains are not exclusively expressed.…”

“…The neural plate (NP) will become the brain and spinal cord, the neural crest (NC) will give rise to most of the peripheral nervous system as well as some non-neural tissues, the preplacodal region (PPR) will contribute to the cranial sensory organs and sensory ganglia, and the epidermis (Epi) will become the skin and its appendages. The process by which these domains arise is believed to involve two main steps: at gastrula stages the embryonic ectoderm is separated into neural and non-neural domains by ventral-to-dorsal (or lateral-tomedial, depending on the animal) gradients of Wnt and BMP signaling, and subsequently the NC and PPR arise at the border between them (reviewed in Stuhlmiller and Garcia-Castro, 2012;Saint-Jeannet and Moody, 2014;Schlosser, 2014;Schlosser et al, 2014;Moody and LaMantia, 2015;Streit, 2018;Seal and Monsoro-Burq, 2020;Thawani and Groves, 2020;Schlosser, 2021). By late neural plate stages, each of the four domains is characterized by a distinct suite of transcription factors (TFs) that are thought to impose domain-specific identity (reviewed in Grocott et al, 2012;Milet and Monsoro-Burq, 2012;Moody and LaMantia, 2015;Streit, 2018;Seal and Monsoro-Burq, 2020;Thawani and Groves, 2020).…”

“…The "binary competence" model posits that due to the expression of different combinations of TFs and region-specific signals, the lateral border of the neural ectoderm becomes competent to give rise to NC and the medial border of the non-neural ectoderm becomes competent to give rise to the PPR (Ahrens and Schlosser, 2005;Schlosser, 2008;Pieper et al, 2012;Schlosser, 2021). The "border state" model posits that interactions between the neural and non-neural ectoderm produce an intermediate neural border zone (NB) that contains common precursors of both NC and PPR, and their domains subsequently separate via differential responses to signals from the underlying tissues and the expression of TFs that are enriched in either the NC or PPR by late neural plate stages (reviewed in Moody and LaMantia, 2015;Seal and Monsoro-Burq, 2020;Thawani and Groves, 2020;Schlosser 2021). This idea is supported by transcriptomic analyses of dissected pieces of ectoderm in frog and chick that showed that at first TFs characteristic of dorsal/midline ectoderm broadly overlap with TFs characteristic of ventral/lateral ectoderm, which by the end of gastrulation resolves into regionally-distinct transcriptional signatures (Hintze et al, 2017;Plouhinec et al, 2017;Trevers et al, 2018).…”

ZEB2, the Mowat-Wilson Syndrome Transcription Factor: Confirmations, Novel Functions, and Continuing Surprises

“…NCCs are a transient embryonic cell lineage originating from the border between the ectoderm and the neuroectoderm under the control of the right dose of BMP-SMAD signaling, all along the anterior-posterior axis of the embryo at its dorsal midline [ 164 , 165 , 166 , 167 , 168 ]. These cells undergo EMT, delaminate, migrate extensively, and differentiate into ectomesenchymal cell types, including neurons and glial cells of the PNS, pigment cells, smooth muscle cells, craniofacial cartilage and bone [ 169 , 170 ], and dental pulp cells [ 171 ].…”