The Protein Tyrosine Phosphatase Receptor Delta Regulates Developmental Neurogenesis
| Autor: | Alejandra R. Alvarez, Cameron L. Woodard, David R. Kaplan, Constanza Rioseco, Hideaki Tomita, Gonzalo I. Cancino, Begoña Aranda-Pino, Freda D. Miller, Francisca Cornejo, Benjamin G. Neel |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Neurogenesis Tropomyosin receptor kinase B Protein tyrosine phosphatase Biology General Biochemistry Genetics and Molecular Biology Receptor tyrosine kinase 03 medical and health sciences 0302 clinical medicine Neural Stem Cells Animals Humans Phosphorylation lcsh:QH301-705.5 Alleles Cells Cultured Cell Proliferation Cerebral Cortex Neurons Gene knockdown Receptor-Like Protein Tyrosine Phosphatases Class 2 Cell Differentiation Matrix Attachment Region Binding Proteins Embryo Mammalian Cell biology Mice Inbred C57BL 030104 developmental biology HEK293 Cells lcsh:Biology (General) Gene Knockdown Techniques biology.protein Signal transduction T-Box Domain Proteins Neural development 030217 neurology & neurosurgery Signal Transduction Transcription Factors |
| Zdroj: | Cell Reports, Vol 30, Iss 1, Pp 215-228.e5 (2020) |
| ISSN: | 2211-1247 |
| Popis: | Summary: PTPRD is a receptor protein tyrosine phosphatase that is genetically associated with neurodevelopmental disorders. Here, we asked whether Ptprd mutations cause aberrant neural development by perturbing neurogenesis in the murine cortex. We show that loss of Ptprd causes increases in neurogenic transit-amplifying intermediate progenitor cells and cortical neurons and perturbations in neuronal localization. These effects are intrinsic to neural precursor cells since acute Ptprd knockdown causes similar perturbations. PTPRD mediates these effects by dephosphorylating receptor tyrosine kinases, including TrkB and PDGFRβ, and loss of Ptprd causes the hyperactivation of TrkB and PDGFRβ and their downstream MEK-ERK signaling pathway in neural precursor cells. Moreover, inhibition of aberrant TrkB or MEK activation rescues the increased neurogenesis caused by knockdown or homozygous loss of Ptprd. These results suggest that PTPRD regulates receptor tyrosine kinases to ensure appropriate numbers of intermediate progenitor cells and neurons, suggesting a mechanism for its genetic association with neurodevelopmental disorders. : Tomita et al. describe how PTPRD, a protein tyrosine phosphatase receptor associated with neurodevelopmental disorders, regulates murine embryonic neurogenesis via the RTK-MEK-ERK signaling pathway. PTPRD null embryos have more intermediate progenitors and, consequently, more cortical neurons, suggesting a mechanism for why loss of PTPRD function results in cognitive dysfunction. Keywords: PTPRD, TrkB, PDGFRβ, MEK, ERK, neural precursor cells, intermediate progenitors, neurogenesis, cortical development, autism spectrum disorders |
| Databáze: | OpenAIRE |
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