Ca²⁺ homeostasis maintained by TMCO1 underlies corpus callosum development via ERK signaling.

ABSTRACT: Transmembrane of coiled-coil domains 1 (TMCO1) plays an important role in maintaining homeostasis of calcium (Ca²⁺) stores in the endoplasmic reticulum (ER). TMCO1-defect syndrome shares multiple features with human cerebro-facio-thoracic (CFT) dysplasia, including abnormal corpus callosum (CC). Here, we report that TMCO1 is required for the normal development of CC through sustaining Ca²⁺ homeostasis. Tmco1^-/- mice exhibit severe agenesis of CC with stalled white matter fiber bundles failing to pass across the midline. Mechanistically, the excessive Ca²⁺ signals caused by TMCO1 deficiency result in upregulation of FGFs and over-activation of ERK, leading to an excess of glial cell migration and overpopulated midline glia cells in the indusium gr

SUBMITTER: Yang KY 

PROVIDER: S-EPMC9352667 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature