| Autor: |
Yacine Touahri, Joseph Hanna, Nobuhiko Tachibana, Satoshi Okawa, Hedy Liu, Luke Ajay David, Thomas Olender, Lakshmy Vasan, Alissa Pak, Dhruv Nimesh Mehta, Vorapin Chinchalongporn, Anjali Balakrishnan, Robert Cantrup, Rajiv Dixit, Pierre Mattar, Fermisk Saleh, Yaroslav Ilnytskyy, Monzur Murshed, Paul E. Mains, Igor Kovalchuk, Julie L. Lefebvre, Hon S. Leong, Michel Cayouette, Chao Wang, Antonio del Sol, Marjorie Brand, Benjamin E. Reese, Carol Schuurmans |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 43, Iss 4, Pp 114005- (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114005 |
| Popis: |
Summary: The retina is exquisitely patterned, with neuronal somata positioned at regular intervals to completely sample the visual field. Here, we show that phosphatase and tensin homolog (Pten) controls starburst amacrine cell spacing by modulating vesicular trafficking of cell adhesion molecules and Wnt proteins. Single-cell transcriptomics and double-mutant analyses revealed that Pten and Down syndrome cell adhesion molecule Dscam) are co-expressed and function additively to pattern starburst amacrine cell mosaics. Mechanistically, Pten loss accelerates the endocytic trafficking of DSCAM, FAT3, and MEGF10 off the cell membrane and into endocytic vesicles in amacrine cells. Accordingly, the vesicular proteome, a molecular signature of the cell of origin, is enriched in exocytosis, vesicle-mediated transport, and receptor internalization proteins in Pten conditional knockout (PtencKO) retinas. Wnt signaling molecules are also enriched in PtencKO retinal vesicles, and the genetic or pharmacological disruption of Wnt signaling phenocopies amacrine cell patterning defects. Pten thus controls vesicular trafficking of cell adhesion and signaling molecules to establish retinal amacrine cell mosaics. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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