TMEM161B regulates cerebral cortical gyration, Sonic Hedgehog signaling, and ciliary structure in the developing central nervous system Article Swipe
Shyam K. Akula
,
Jack H. Marciano
,
Youngshin Lim
,
David Exposito-Alonso
,
Norma K. Hylton
,
Grace H. Hwang
,
Jennifer E. Neil
,
Nicole Dominado
,
Rosie Bunton-Stasyshyn
,
Janet 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 Clark
,
Carlos A. Bacino
,
Richard A. Lewis
,
Rosalind A. Segal
,
J. Fernando Bazán
,
K. A. Smith
,
Jeffrey A. Golden
,
Ginam Cho
,
Christopher A. Walsh
,
David R. Adams
,
Aaron W. Aday
,
Mercedes E. Alejandro
,
Patrick Allard
,
Euan A. Ashley
,
Mahshid S. Azamian
,
Carlos A. Bacino
,
Eva H. Baker
,
Ashok Balasubramanyam
,
Hayk Barseghyan
,
Gabriel F. Batzli
,
Alan H. Beggs
,
Babak Behnam
,
Hugo J. Bellen
,
Jonathan A. Bernstein
,
Gerard T. Berry
,
Anna Bican
,
David Bick
,
Camille L. Birch
,
Devon Bonner
,
Braden Boone
,
Bret L. Bostwick
,
Lauren C. Briere
,
Elly Brokamp
,
Donna M. Brown
,
Matthew Brush
,
Elizabeth A. Burke
,
Lindsay C. Burrage
,
Manish J. Butte
,
Shan Chen
,
Gary Clark
,
Terra R. Coakley
,
Laurel A. Cobban
,
Joy D. Cogan
,
Heather A. Colley
,
Cynthia M. Cooper
,
Heidi Cope
,
William J. Craigen
,
Precilla D’Souza
,
Mariska Davids
,
Jean M. Davidson
,
Jyoti G. Dayal
,
Esteban C. Dell’Angelica
,
Shweta U. Dhar
,
Katrina M. Dipple
,
Naghmeh Dorrani
,
Daniel C. Dorset
,
Jessica Douglas
,
Emilie D. Douine
,
David D. Draper
,
Annika M. Dries
,
David J. Eckstein
,
Lisa Emrick
,
Christine M. Eng
,
Gregory M. Enns
,
Ascia Eskin
,
Cecilia Esteves
,
Tyra Estwick
,
Liliana Fernández
,
Carlos R. Ferreira
,
Elizabeth L. Fieg
,
Paul G. Fisher
,
Brent L. Fogel
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2209964120
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2209964120
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. Tmem161b depletion impaired the response to Smoothened activation in vitro and disrupted cortical histogenesis in vivo 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 Tmem161b null mouse, suggesting that the Shh-related phenotypes may reflect ciliary dysfunction. Our data identify TMEM161B 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.
Related Topics
Concepts
Sonic hedgehog
Cilium
Biology
Cell biology
Axon guidance
Smoothened
Hedgehog signaling pathway
Neuroscience
GLI3
Anatomy
Signal transduction
Genetics
Axon
Transcription factor
Gene
Repressor
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1073/pnas.2209964120
- OA Status
- hybrid
- Cited By
- 23
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4317600508
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4317600508Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1073/pnas.2209964120Digital Object Identifier
- Title
-
TMEM161B regulates cerebral cortical gyration, Sonic Hedgehog signaling, and ciliary structure in the developing central nervous systemWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-01-20Full publication date if available
- Authors
-
Shyam K. Akula, Jack H. Marciano, Youngshin Lim, David Exposito-Alonso, Norma K. Hylton, Grace H. Hwang, Jennifer E. Neil, Nicole Dominado, Rosie Bunton-Stasyshyn, Janet 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 Clark, Carlos A. Bacino, Richard A. Lewis, Rosalind A. Segal, J. Fernando Bazán, K. A. Smith, Jeffrey A. Golden, Ginam Cho, Christopher A. Walsh, David R. Adams, Aaron W. Aday, Mercedes E. Alejandro, Patrick Allard, Euan A. Ashley, Mahshid S. Azamian, Carlos A. Bacino, Eva H. Baker, Ashok Balasubramanyam, Hayk Barseghyan, Gabriel F. Batzli, Alan H. Beggs, Babak Behnam, Hugo J. Bellen, Jonathan A. Bernstein, Gerard T. Berry, Anna Bican, David Bick, Camille L. Birch, Devon Bonner, Braden Boone, Bret L. Bostwick, Lauren C. Briere, Elly Brokamp, Donna M. Brown, Matthew Brush, Elizabeth A. Burke, Lindsay C. Burrage, Manish J. Butte, Shan Chen, Gary Clark, Terra R. Coakley, Laurel A. Cobban, Joy D. Cogan, Heather A. Colley, Cynthia M. Cooper, Heidi Cope, William J. Craigen, Precilla D’Souza, Mariska Davids, Jean M. Davidson, Jyoti G. Dayal, Esteban C. Dell’Angelica, Shweta U. Dhar, Katrina M. Dipple, Naghmeh Dorrani, Daniel C. Dorset, Jessica Douglas, Emilie D. Douine, David D. Draper, Annika M. Dries, David J. Eckstein, Lisa Emrick, Christine M. Eng, Gregory M. Enns, Ascia Eskin, Cecilia Esteves, Tyra Estwick, Liliana Fernández, Carlos R. Ferreira, Elizabeth L. Fieg, Paul G. Fisher, Brent L. FogelList of authors in order
- Landing page
-
https://doi.org/10.1073/pnas.2209964120Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
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hybridOpen access status per OpenAlex
- OA URL
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https://doi.org/10.1073/pnas.2209964120Direct OA link when available
- Concepts
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Sonic hedgehog, Cilium, Biology, Cell biology, Axon guidance, Smoothened, Hedgehog signaling pathway, Neuroscience, GLI3, Anatomy, Signal transduction, Genetics, Axon, Transcription factor, Gene, RepressorTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
23Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 7, 2024: 10, 2023: 6Per-year citation counts (last 5 years)
- References (count)
-
53Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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