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  Primary cilia signaling promotes axonal tract development and is disrupted in Joubert Syndrome-related disorder models.

Guo, J., Otis, J. M., Suciu, S. K., Catalano, C., Xing, L., Constable, S., et al. (2019). Primary cilia signaling promotes axonal tract development and is disrupted in Joubert Syndrome-related disorder models. Developmental Cell, 51(6): e5, pp. 759-774. doi:10.1016/j.devcel.2019.11.005.

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GuoWachten_PrimaryCiliaSignaling_MolPhys_2019.pdf (Publisher version), 7MB
 
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 Creators:
Guo, Jiami1, Author
Otis, James M.1, Author
Suciu, Sarah K.1, Author
Catalano, Christy1, Author
Xing, Lei1, Author
Constable, Sandii1, Author
Wachten, Dagmar2, Author           
Gupton, Stephanie1, Author
Lee, Janice1, Author
Lee, Amelia1, Author
Blackley, Katherine H.1, Author
Ptacek, Travis1, Author
Simon, Jeremy M.1, Author
Schurmans, Stephane1, Author
Stuber, Garret D.1, Author
Caspary, Tamara1, Author
Anton, E.S.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Research Group Molecular Physiology, Center of Advanced European Studies and Research (caesar), Max Planck Society, ou_2173682              

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Free keywords: Joubert syndrome-related disorders; axonal pathways; brain development; brain wiring; ciliopathies; connectome; molar tooth sign; optogenetic activation of primary cilia; primary cilia; projection neurons
 Abstract: Appropriate axonal growth and connectivity are essential for functional wiring of the brain. Joubert syndrome-related disorders (JSRD), a group of ciliopathies in which mutations disrupt primary cilia function, are characterized by axonal tract malformations. However, little is known about how cilia-driven signaling regulates axonal growth and connectivity. We demonstrate that the deletion of related JSRD genes, Arl13b and Inpp5e, in projection neurons leads to de-fasciculated and misoriented axonal tracts. Arl13b deletion disrupts the function of its downstream effector, Inpp5e, and deregulates ciliary-PI3K/AKT signaling. Chemogenetic activation of ciliary GPCR signaling and cilia-specific optogenetic modulation of downstream second messenger cascades (PI3K, AKT, and AC3) commonly regulated by ciliary signaling receptors induce rapid changes in axonal dynamics. Further, Arl13b deletion leads to changes in transcriptional landscape associated with dysregulated PI3K/AKT signaling. These data suggest that ciliary signaling acts to modulate axonal connectivity and that impaired primary cilia signaling underlies axonal tract defects in JSRD.

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Language(s): eng - English
 Dates: 2019-12-16
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.devcel.2019.11.005
PMID: 31846650
 Degree: -

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Title: Developmental Cell
  Abbreviation : Dev Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 51 (6) Sequence Number: e5 Start / End Page: 759 - 774 Identifier: ISSN: 1534-5807
CoNE: https://pure.mpg.de/cone/journals/resource/111006902714134