Abstract
The embryonic ectoderm is composed of four domains: neural plate, neural crest, pre-placodal region (PPR) and epidermis. Their formation is initiated during early gastrulation by dorsal-ventral and anterior-posterior gradients of signaling factors that first divide the embryonic ectoderm into neural and non-neural domains. Next, the neural crest and PPR domains arise, either via differential competence of the neural and non-neural ectoderm (binary competence model) or via interactions between the neural and non-neural ectoderm tissues to produce an intermediate neural border zone (NB) (border state model) that subsequently separates into neural crest and PPR. Many previous gain- and loss-of-function experiments demonstrate that numerous TFs are expressed in initially overlapping zones that gradually resolve into patterns that by late neurula stages are characteristic of each of the four domains. Several of these studies suggested that this is accomplished by a combination of repressive TF interactions and competence to respond to local signals. In this study, we ectopically expressed TFs that at neural plate stages are characteristic of one domain in a different domain to test whether they act cell autonomously as repressors. We found that almost all tested TFs caused reduced expression of the other TFs. At gastrulation these effects were strictly within the lineage-labeled cells, indicating that the effects were cell autonomous, i.e., due to TF interactions within individual cells. Analysis of previously published single cell RNAseq datasets showed that at the end of gastrulation, and continuing to neural tube closure stages, many ectodermal cells express TFs characteristic of more than one neural plate stage domain, indicating that different TFs have the opportunity to interact within the same cell. At neurula stages repression was observed both in the lineage-labeled cells and in adjacent cells not bearing detectable lineage label, suggesting that cell-to-cell signaling has begun to contribute to the separation of the domains. Together, these observations directly demonstrate previous suggestions in the literature that the segregation of embryonic ectodermal domains initially involves cell autonomous, repressive TF interactions within an individual cell followed by the subsequent advent of non-cell autonomous signaling to neighbors.
Highlights
After gastrulation is completed, the vertebrate embryonic ectoderm is composed of four distinct domains with different fates
Many previous studies showed that as the embryonic ectoderm gradually resolves into four distinct domains, numerous transcription factors (TFs) are expressed in overlapping patterns that eventually segregate during neurulation into neural plate (NP), neural crest (NC), preplacodal region (PPR) and Epi, each of which characteristically expresses a subset of these TFs
While previous studies focused on sox2 and sox3 as NP specifiers, we uniquely focused on the forkhead transcription factor Foxd4l1.1, referred to as Foxd4, because of its three advantages
Summary
After gastrulation is completed, the vertebrate embryonic ectoderm is composed of four distinct domains with different fates. 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). The acquisition of distinct NP, NC, PPR and Epi fates appears to be a gradual process that involves, at least in part, TF interactions that eventually segregate domains
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