Integrative computational analyses implicate regulatory genomic elements contributing to spina bifida.

Purpose: Spina bifida (SB) arises from complex genetic interactions that converge to interfere with neural tube closure. Understanding the precise patterns conferring SB risk requires a deep exploration of the genomic networks and molecular pathways that govern neurulation. This study aims to delineate genome-wide regulatory signatures underlying SB pathophysiology.

The DNA demethylase TET1 modifies the impact of maternal folic acid status on embryonic brain development.

Folic acid (FA) is well known to prevent neural tube defects (NTDs), but we do not know why many human NTD cases still remain refractory to FA supplementation. Here, we investigate how the DNA demethylase TET1 interacts with maternal FA status to regulate mouse embryonic brain development. We determined that cranial NTDs display higher penetrance in non-inbred than in inbred Tet1 embryos and are resistant to FA supplementation across strains.

Compound heterozygous mutation of AFG3L2 causes autosomal recessive spinocerebellar ataxia through mitochondrial impairment and MICU1 mediated Ca overload.

Autosomal recessive spinocerebellar ataxias (SCARs) are one of the most common neurodegenerative diseases characterized by progressive ataxia. Although SCARs are known to be caused by mutations in multiple genes, there are still many cases that go undiagnosed or are misdiagnosed. In this study, we presented a SCAR patient, and identified a probable novel pathogenic mutation (c.

Linkage between Fuz and Gpr161 genes regulates sonic hedgehog signaling during mouse neural tube development.

Sonic hedgehog (Shh) signaling regulates embryonic morphogenesis utilizing the primary cilium, the cell's antenna, which acts as a signaling hub. Fuz, an effector of planar cell polarity signaling, regulates Shh signaling by facilitating cilia formation, and the G protein-coupled receptor 161 (Gpr161) is a negative regulator of Shh signaling. The range of phenotypic malformations observed in mice bearing mutations in either of the genes encoding these proteins is similar; however, their functional relationship has not been previously explored.