The NuRD component CHD3 promotes BMP signalling during cranial neural crest cell specification

Area of Science:

• Developmental Biology
• Genetics
• Stem Cell Biology

Background:

• Snijders Blok-Campeau Syndrome is a neurodevelopmental disorder linked to genetic variants in CHD3.
• Craniofacial anomalies are a key feature of this syndrome, indicating a role for CHD3 in head development.

Purpose of the Study:

• To investigate the function of CHD3 in craniofacial development.
• To elucidate the molecular mechanisms by which CHD3 regulates cranial neural crest cell (CNCC) specification.

Main Methods:

• Differentiation of human-induced pluripotent stem cells (hiPSCs) with and without CHD3 depletion into CNCCs.
• Analysis of gene expression, chromatin accessibility, and signaling pathway activity (BMP and Wnt).

Main Results:

• CHD3 is upregulated during early CNCC specification and enhances BMP signaling by modulating chromatin accessibility at BMP-responsive elements.
• CHD3 depletion leads to repressed BMP target genes, reduced chromatin accessibility, and an imbalance between BMP and Wnt signaling.
• Loss of CHD3 function results in failed CNCC specification and aberrant early-mesoderm identity, partially reversible by adjusting Wnt signaling levels.

Conclusions:

• CHD3 is a critical regulator of BMP signaling essential for proper neural crest specification and craniofacial development.
• The findings provide a molecular basis for the craniofacial anomalies observed in Snijders Blok-Campeau Syndrome.