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Journal article
Rpsa Signaling Regulates Cortical Neuronal Morphogenesis via Its Ligand, PEDF, and Plasma Membrane Interaction Partner, Itga6
Cerebral cortex (New York, N.Y. 1991), v 32(4), pp 770-795
08 Feb 2022
PMID: 34347028
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Neuromorphological defects underlie neurodevelopmental disorders and functional defects. We identified a function for Rpsa in regulating neuromorphogenesis using in utero electroporation to knockdown Rpsa, resulting in apical dendrite misorientation, fewer/shorter extensions, and decreased spine density with altered spine morphology in upper neuronal layers and decreased arborization in upper/lower cortical layers. Rpsa knockdown disrupts multiple aspects of cortical development, including radial glial cell fiber morphology and neuronal layering. We investigated Rpsa's ligand, PEDF, and interacting partner on the plasma membrane, Itga6. Rpsa, PEDF, and Itga6 knockdown cause similar phenotypes, with Rpsa and Itga6 overexpression rescuing morphological defects in PEDF-deficient neurons in vivo. Additionally, Itga6 overexpression increases and stabilizes Rpsa expression on the plasma membrane. GCaMP6s was used to functionally analyze Rpsa knockdown via ex vivo calcium imaging. Rpsa-deficient neurons showed less fluctuation in fluorescence intensity, suggesting defective subthreshold calcium signaling. The Serpinf1 gene coding for PEDF is localized at chromosome 17p13.3, which is deleted in patients with the neurodevelopmental disorder Miller-Dieker syndrome. Our study identifies a role for Rpsa in early cortical development and for PEDF-Rpsa-Itga6 signaling in neuromorphogenesis, thus implicating these molecules in the etiology of neurodevelopmental disorders like Miller-Dieker syndrome and identifying them as potential therapeutics.
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- Title
- Rpsa Signaling Regulates Cortical Neuronal Morphogenesis via Its Ligand, PEDF, and Plasma Membrane Interaction Partner, Itga6
- Creators
- Sara M Blazejewski - Drexel UniversitySarah A Bennison - Drexel UniversityNgoc T Ha - Drexel UniversityXiaonan Liu - Drexel UniversityTrevor H Smith - Drexel UniversityKimberly J Dougherty - Drexel UniversityKazuhito Toyo-Oka (Corresponding Author) - Drexel University
- Publication Details
- Cerebral cortex (New York, N.Y. 1991), v 32(4), pp 770-795
- Publisher
- Oxford University Press
- Grant note
- F31 NS113404 / NINDS NIH HHS F31 HD103405 / NICHD NIH HHS R01 NS095366 / NINDS NIH HHS R01 NS096098 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pharmacology and Physiology
- Web of Science ID
- WOS:000776233100001
- Scopus ID
- 2-s2.0-85124576578
- Other Identifier
- 991019169641304721
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- Web of Science research areas
- Neurosciences