Shyam K Akula, Jack H Marciano, Youngshin Lim, David Exposito-Alonso, Norma K Hylton, Grace H Hwang, Jennifer E Neil, Nicole Dominado, Rosie K Bunton-Stasyshyn, Janet H T Song, Maya Talukdar, Aloisia Schmid, Lydia Teboul, Alisa Mo, Taehwan Shin, Benjamin Finander, Samantha G Beck, Rebecca C Yeh, Aoi Otani, Xuyu Qian, Ellen M DeGennaro, Fowzan S Alkuraya, Sateesh Maddirevula, Gregory D Cascino, Caterina Giannini, Lindsay C Burrage, Jill A Rosenfield, Shamika Ketkar, Gary D Clark, Carlos Bacino, Richard A Lewis, Rosalind A Segal, J Fernando Bazan, Kelly A Smith, Jeffrey A Golden, Ginam Cho, Christopher A Walsh
Sonic hedgehog signaling regulates processes of embryonic development across multiple tissues, yet factors regulating context-specific Shh signaling remain poorly understood. Exome sequencing of families with polymicrogyria (disordered cortical folding) revealed multiple individuals with biallelic deleterious variants in TMEM161B , which encodes a multi-pass transmembrane protein of unknown function. Tmem161b null mice demonstrated holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes consistent with impaired Shh signaling, but were without limb defects, suggesting a CNS-specific role of Tmem161b...
January 24, 2023: Proceedings of the National Academy of Sciences of the United States of America