Document Type
Article
Publication Date
1-24-2023
Original Citation
Wang L,
Heffner C,
Vong K,
Barrows C,
Ha Y,
Lee S,
Lara-Gonzalez P,
Jhamb I,
Van Der Meer D,
Loughnan R,
Parker N,
Sievert D,
Mittal S,
Issa M,
Andreassen O,
Dale A,
Dobyns W,
Zaki M,
Murray S,
Gleeson J.
TMEM161B modulates radial glial scaffolding in neocortical development. Proc Natl Acad Sci U S A. 2023;120(4):e2209983120.
Keywords
Animals, Humans, Mice, Ependymoglial Cells, Mice, Knockout, Neocortex
JAX Source
Proc Natl Acad Sci U S A. 2023;120(4):e2209983120.
ISSN
1091-6490
PMID
36669109
DOI
https://doi.org/10.1073/pnas.2209983120
Grant
L.W. received support from NIH/NINDS Pathway to inde- pendent K99/R00 award (1K99NS125106-01A1), CIRM Training Grant Postdoc
Abstract
TMEM161B encodes an evolutionarily conserved widely expressed novel 8-pass trans- membrane protein of unknown function in human. Here we identify TMEM161B homozygous hypomorphic missense variants in our recessive polymicrogyria (PMG) cohort. Patients carrying TMEM161B mutations exhibit striking neocortical PMG and intellectual disability. Tmem161b knockout mice fail to develop midline hem- ispheric cleavage, whereas knock-in of patient mutations and patient-derived brain organoids show defects in apical cell polarity and radial glial scaffolding. We found that TMEM161B modulates actin filopodia, functioning upstream of the Rho-GTPase CDC42. Our data link TMEM161B with human PMG, likely regulating radial glia apical polarity during neocortical development.
Comments
This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).