BMP signaling is enhanced intracellularly by FHL3 controlling WNT-dependent spatiotemporal emergence of the neural crest

Abstract

Highlights d Fhl3 is an intracellular enhancer of BMP signaling during early development d In vivo Fhl3 synergizes with moderate BMP levels and promotes wnt8 activation d Fhl3 controls the dynamics of BMP and Wnt levels triggering neural crest d Reiterated Fhl3 action in mesoderm/ectoderm impacts two steps of the neural crest GRN

Review: The Role of Wnt/β-Catenin Signalling in Neural Crest Development in Zebrafish

“…More recently, BMP responsive elements were identified upstream of the transcriptional start site of wnt8 . The transcriptional activator of the BMP signalling pathway, Smad1, was able to bind these cis -regulatory elements in the presence of a scaffold protein, Fhl3 ( Alkobtawi et al, 2021 ). A further interaction has been reported on the level of the secreted BMP antagonist Gremlin ( Pegge et al, 2020 ), which interacts with heparan sulfate proteoglycans (HSPGs), a family of cell surface macromolecules that regulate Wnt distribution and signalling (reviewed in Routledge and Scholpp, 2019 ).…”

From neural border to migratory stage: A comprehensive single cell roadmap of the timing and regulatory logic driving cranial and vagal neural crest emergence

“…Interestingly, no direct route was found between nne1 and nc (Fig. 7D), or between ne and pc (Fig.7G), retrieving known biological features, such as the partial neuralization needed for NC induction or the close link between placodes and NNE ( 17, 18 ). Because current tools cannot assess multiple branching simultaneously, we applied branching analysis for each potential developmental route in order to define and compare the gene programs underlying NC vs PC fate decisions along each route.…”

“…Using deeper re-sequencing of single cell (SC) series from whole X. tropicalis embryos (17), taken at 8 consecutive developmental stages, followed by updated genome annotation and alignment, we have scrutinized 17138 early dorsal ectoderm cells and 6135 neural crest (NC) cells from early gastrulation stage to post-EMT early migration stage. The large cell number of our new dataset permits assessment of the cellular diversity in the NC population during early induction (at late gastrulation stages 12-13 and neural plate stages [13][14], during neural fold elevation (stages [16][17][18], during EMT (neural tube stages [18][19][20] and at the earliest stages of NC cells emigration (tailbud stage 22).…”

“…During gastrulation (stages [11][12][13], the neural plate and the neural border zone are induced from the dorsal ectoderm due to BMP antagonists in the midline and Wnt/FGF signaling from the underlying mesoderm (18). As early as stage 10.5-11, the neural border initiates a few distinct gene expressions, such as pax3/7 (19).…”

“…We tested it on another vertebrate organism, zebrafish, to evaluate its accuracy for NC annotation. Our binary classifier determined whether a cell was NC or not, using our annotated frog whole embryo dataset at seven developmental stages (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). The algorithm was tested on a zebrafish whole embryo SC dataset (21) at stage 14hpf (equivalent to frog stage 22) with a result of 0.95 for AUC score and 0.66 for F1 score (F1 score defines the weighted harmonic mean of the precision and recall, and it is equal to 0.05 for a random model applied to the zebrafish dataset, Fig.…”