Pax3 Lineage-Specific Deletion of Gpr161 Is Associated With Spinal Neural Tube and Craniofacial Malformations During Embryonic Development

Authors

Sung-Eun Kim
Pooja J Chothani
Rehana Shaik
Westley Pollard
Richard H Finnell

Publication Date

11-1-2023

Journal

Disease Models & Mechanisms

DOI

10.1242/dmm.050277

PMID

37885410

PMCID

PMC10694864

PubMedCentral® Posted Date

11-28-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Mice, Animals, Neural Tube, Hedgehog Proteins, Transcription Factors, Spinal Dysraphism, Embryonic Development, Wnt Signaling Pathway, Neurogenesis, Spine, Gpr161, Pax3, Wnt/β-catenin signaling, Craniofacial development, Spinal neural tube

Abstract

Sonic hedgehog (Shh) signaling is the morphogen signaling that regulates embryonic craniofacial and neural tube development. G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling, and its inactivation in mice results in embryo lethality associated with craniofacial defects and neural tube defects. However, the structural defects of later embryonic stages and cell lineages underlying abnormalities have not been well characterized due to the limited lifespan of Gpr161 null mice. We found that embryos with Pax3 lineage-specific deletion of Gpr161 presented with tectal hypertrophy (anterior dorsal neuroepithelium), cranial vault and facial bone hypoplasia (cranial neural crest), vertebral abnormalities (somite) and the closed form of spina bifida (posterior dorsal neuroepithelium). In particular, the closed form of spina bifida was partly due to reduced Pax3 and Cdx4 gene expression in the posterior dorsal neural tubes of Gpr161 mutant embryos with decreased Wnt signaling, whereas Shh signaling was increased. We describe a previously unreported role for Gpr161 in the development of posterior neural tubes and confirm its role in cranial neural crest- and somite-derived skeletogenesis and midbrain morphogenesis in mice.

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