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Sci Rep November 15, 2017; 7 (1): 15623.

A Nonredundant Role for the TRPM6 Channel in Neural Tube Closure.

Komiya Y , Bai Z , Cai N , Lou L , Al-Saadi N , Mezzacappa C , Habas R , Runnels LW .

In humans, germline mutations in Trpm6 cause autosomal dominant hypomagnesemia with secondary hypocalcemia disorder. Loss of Trpm6 in mice also perturbs cellular magnesium homeostasis but additionally results in early embryonic lethality and neural tube closure defects. To define the mechanisms by which TRPM6 influences neural tube closure, we functionally characterized the role of TRPM6 during early embryogenesis in Xenopus laevis. The expression of Xenopus TRPM6 (XTRPM6) is elevated at the onset of gastrulation and is concentrated in the lateral mesoderm and ectoderm at the neurula stage. Loss of XTRPM6 produced gastrulation and neural tube closure defects. Unlike XTRPM6''s close homologue XTRPM7, whose loss interferes with mediolateral intercalation, depletion of XTRPM6 but not XTRPM7 disrupted radial intercalation cell movements. A zinc-influx assay demonstrated that TRPM6 has the potential to constitute functional channels in the absence of TRPM7. The results of our study indicate that XTRPM6 regulates radial intercalation with little or no contribution from XTRPM7 in the region lateral to the neural plate, whereas XTRPM7 is mainly involved in regulating mediolateral intercalation in the medial region of the neural plate. We conclude that both TRPM6 and TRPM7 channels function cooperatively but have distinct and essential roles during neural tube closure.

PubMed ID: 29142255
PMC ID: PMC5688082
Article link: Sci Rep
Grant support: [+]
Genes referenced: dvl2 odc1 otx2 sox2 trpm6 trpm7
Morpholinos: trpm6 MO2 trpm7 MO4

Article Images: [+] show captions
References [+] :
Abiria, TRPM7 senses oxidative stress to release Zn2+ from unique intracellular vesicles. 2017, Pubmed

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