TMEM161B modulates radial glial scaffolding in neocortical development.
Lu WangCaleb HeffnerKeng Ioi VongChelsea BarrowsYoo-Jin HaSangmoon LeePablo Lara-GonzalezIshani JhambDennis Van Der MeerRobert LoughnanNadine ParkerDavid SievertSwapnil MittalMahmoud Y IssaOle Andreas AndreassenAnders M DaleWilliam B DobynsMaha Saad ZakiStephen A MurrayJoseph G GleesonPublished in: Proceedings of the National Academy of Sciences of the United States of America (2023)
TMEM161B encodes an evolutionarily conserved widely expressed novel 8-pass transmembrane 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 hemispheric 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.
Keyphrases
- intellectual disability
- endothelial cells
- autism spectrum disorder
- end stage renal disease
- chronic kidney disease
- ejection fraction
- neuropathic pain
- newly diagnosed
- single cell
- electronic health record
- stem cells
- transcription factor
- spinal cord injury
- cell cycle
- gene expression
- cell proliferation
- small molecule
- brain injury
- mesenchymal stem cells
- big data
- resting state
- spinal cord
- bone marrow
- patient reported outcomes
- amino acid
- cell migration