| First Author | Tomita H | Year | 2020 |
| Journal | Cell Rep | Volume | 30 |
| Issue | 1 | Pages | 215-228.e5 |
| PubMed ID | 31914388 | Mgi Jnum | J:287484 |
| Mgi Id | MGI:6415470 | Doi | 10.1016/j.celrep.2019.11.033 |
| Citation | Tomita H, et al. (2020) The Protein Tyrosine Phosphatase Receptor Delta Regulates Developmental Neurogenesis. Cell Rep 30(1):215-228.e5 |
| abstractText | 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 PDGFRbeta, and loss of Ptprd causes the hyperactivation of TrkB and PDGFRbeta 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. |
