TMEM161B modulates radial glial scaffolding in neocortical development-Reference-Cited by-同舟云学术

TMEM161B modulates radial glial scaffolding in neocortical development

Published:2023-01-20 Issue:4 Volume:120 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Wang Lu¹²^ORCID,Heffner Caleb³^ORCID,Vong Keng loi¹²^ORCID,Barrows Chelsea¹²,Ha Yoo-Jin¹⁴,Lee Sangmoon¹²,Lara-Gonzalez Pablo⁵^ORCID,Jhamb Ishani¹²,Van Der Meer Dennis⁶,Loughnan Robert⁷,Parker Nadine⁶,Sievert David¹²,Mittal Swapnil¹²,Issa Mahmoud Y.⁸^ORCID,Andreassen Ole A.⁶^ORCID,Dale Anders¹⁶⁷^ORCID,Dobyns William B.⁹,Zaki Maha S.⁸^ORCID,Murray Stephen A.³^ORCID,Gleeson Joseph G.¹²^ORCID

Affiliation:

1. Department of Neurosciences, University of California San Diego, La Jolla, CA 92093

2. Rady Children’s Institute for Genomic Medicine, Rady Children’s Hospital, San Diego, CA 92123

3. The Jackson Laboratory, Bar Harbor, ME, 04609

4. Department of Biomedical Systems Informatics, Yonsei University, Seoul 03722, S. Korea

5. Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA 92697

6. Norwegian Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo 0424, Norway

7. The Department of Cognitive Science, University of California San Diego, La Jolla, CA 92093

8. Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo 12311, Egypt

9. Department of Pediatrics, Division of Genetics and Metabolism, University of Minnesota, Minneapolis, MN 55455

Abstract

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.

Funder

Brain and Behavior Research Foundation

HHS | NIH | National Human Genome Research Institute

HHS | NIH | National Institute of Neurological Disorders and Stroke

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2209983120

Reference38 articles.

1. Trnp1 Regulates Expansion and Folding of the Mammalian Cerebral Cortex by Control of Radial Glial Fate