[en] 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 moleculeDscam) 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.
Disciplines :
Sciences du vivant: Multidisciplinaire, généralités & autres
Auteur, co-auteur :
Touahri, Yacine ✱; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada, Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada
Hanna, Joseph; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
Tachibana, Nobuhiko; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada
Liu, Hedy; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada
David, Luke Ajay; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
Olender, Thomas; Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada
Vasan, Lakshmy; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
Pak, Alissa; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
Mehta, Dhruv Nimesh; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada, Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada
Chinchalongporn, Vorapin; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada
Balakrishnan, Anjali; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada, Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada
Cantrup, Robert; Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada
Dixit, Rajiv; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada
Mattar, Pierre; Cellular Neurobiology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada
Saleh, Fermisk; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada
Ilnytskyy, Yaroslav; Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada
Murshed, Monzur; Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC H3G 1A6, Canada
Mains, Paul E; Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada
Kovalchuk, Igor; Department of Biological Sciences, University of Lethbridge, Lethbridge, AB T1K 3M4, Canada
Lefebvre, Julie L; Department of Molecular Genetics, University of Toronto, Toronto ON M5S 1A8, Canada, Program for Neuroscience and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
Leong, Hon S; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada
Cayouette, Michel; Cellular Neurobiology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montreal, QC H2W 1R7, Canada
Wang, Chao; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Immunology, University of Toronto, Toronto, ON M5G 1L7, Canada
DEL SOL MESA, Antonio ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Computational Biology
Brand, Marjorie; Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON K1H 8L6, Canada
Reese, Benjamin E; Department of Psychological and Brain Sciences, Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106-5060, USA
Schuurmans, Carol ✱; Biological Sciences Platform, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada, Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada, Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON M5T 3A9, Canada, Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada, Department of Biochemistry and Molecular Biology, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada. Electronic address: cschuurm@sri.utoronto.ca
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