A direct role for murine Cdx proteins in the trunk neural crest gene regulatory network

Area of Science:

• Developmental Biology
• Genetics
• Neuroscience

Background:

• Cdx proteins are known for their ancestral role in organizing post-head tissues in chordates and arthropods.
• Loss of Cdx function in urochordates affects axial elongation, neural tube closure, and pigment cell development.
• A specific role for Cdx in neural crest-derived pigment cell development has not been previously established in other chordates.

Purpose of the Study:

• To investigate the role of Cdx proteins in mammalian neural crest development.
• To overcome challenges of functional redundancy and embryonic lethality in Cdx mutant models.
• To elucidate the direct targets and regulatory network controlled by Cdx proteins in neural crest ontogenesis.

Main Methods:

• Generation of a conditional pan-Cdx functional knockdown mouse model.
• Directed inhibition of Cdx function in the neuroectoderm.
• Analysis of melanocyte and enteric nervous system development.
• Assessment of key neural crest regulators (Pax3, Msx1, Foxd3) expression.

Main Results:

• Murine Cdx proteins directly regulate the expression of Pax3, Msx1, and Foxd3, key regulators of neural crest development.
• Cdx proteins impact melanocyte and enteric nervous system development in vivo.
• This study establishes a novel role for Cdx proteins in the mammalian neural crest gene regulatory network.

Conclusions:

• Cdx proteins play a significant role in the development of melanocytes and the enteric nervous system in mice.
• This function appears to be conserved from ancestral orthologs.
• Cdx proteins act at a high level within the trunk neural crest gene regulatory network.