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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,1,24]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>TMEM161B<\/jats:italic>\n                    , which encodes a multi-pass transmembrane protein of unknown function.\n                    <jats:italic>Tmem161b<\/jats:italic>\n                    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.\n                    <jats:italic>Tmem161b<\/jats:italic>\n                    depletion impaired the response to Smoothened activation in\u00a0vitro and disrupted cortical histogenesis in\u00a0vivo in both mouse and ferret models, including leading to abnormal gyration in the ferret model. Tmem161b localizes non-exclusively to the primary cilium, and scanning electron microscopy revealed shortened, dysmorphic, and ballooned ventricular zone cilia in the\n                    <jats:italic>Tmem161b<\/jats:italic>\n                    null mouse, suggesting that the Shh-related phenotypes may reflect ciliary dysfunction. Our data identify\n                    <jats:italic>TMEM161B<\/jats:italic>\n                    as a regulator of cerebral cortical gyration, as involved in primary ciliary structure, as a regulator of Shh signaling, and further implicate Shh signaling in human gyral development.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2209964120","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T15:09:27Z","timestamp":1674227367000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":30,"title":["TMEM161B regulates cerebral cortical gyration, Sonic Hedgehog signaling, and ciliary structure in the developing central nervous system"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2334-591X","authenticated-orcid":false,"given":"Shyam K.","family":"Akula","sequence":"first","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard-Massachusetts Institute of Technology MD\/PhD Program, Program in Neuroscience, Harvard Medical School, Boston, MA 02115"},{"name":"Howard Hughes Medical Institute, Boston Children\u2019s Hospital Boston, Boston, MA 02115"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115"},{"name":"Department of Neurology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0238-9916","authenticated-orcid":false,"given":"Jack H.","family":"Marciano","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Howard Hughes Medical Institute, Boston Children\u2019s Hospital Boston, Boston, MA 02115"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115"},{"name":"Department of Neurology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7842-3244","authenticated-orcid":false,"given":"Youngshin","family":"Lim","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Howard Hughes Medical Institute, Boston Children\u2019s Hospital Boston, Boston, MA 02115"},{"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4950-2744","authenticated-orcid":false,"given":"David","family":"Exposito-Alonso","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Howard Hughes Medical Institute, Boston Children\u2019s Hospital Boston, Boston, MA 02115"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115"},{"name":"Department of Neurology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norma K.","family":"Hylton","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Harvard-Massachusetts Institute of Technology MD\/PhD Program, Program in Neuroscience, Harvard Medical School, Boston, MA 02115"},{"name":"Howard Hughes Medical Institute, Boston Children\u2019s Hospital Boston, Boston, MA 02115"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115"},{"name":"Department of Neurology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4979-4409","authenticated-orcid":false,"given":"Grace H.","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115"},{"name":"Department of Neurobiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Neil","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children\u2019s Hospital, Boston, MA 02115"},{"name":"Howard Hughes Medical Institute, Boston Children\u2019s Hospital Boston, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Dominado","sequence":"additional","affiliation":[{"name":"Department of Anatomy &amp; 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