| First Author | Bashford AL | Year | 2022 |
| Journal | Hum Mol Genet | Volume | 31 |
| Issue | 19 | Pages | 3245-3265 |
| PubMed ID | 35470378 | Mgi Jnum | J:334106 |
| Mgi Id | MGI:7444605 | Doi | 10.1093/hmg/ddac095 |
| Citation | Bashford AL, et al. (2022) Hippocampals neurogenesis is impaired in mice with a deletion in the coiled coil domain of Talpid3-implications for Joubert syndrome. Hum Mol Genet 31(19):3245-3265 |
| abstractText | Mutations in Talpid3, a basal body protein essential for the assembly of primary cilia, have been reported to be causative for Joubert Syndrome (JS). Herein, we report prominent developmental defects in the hippocampus of a conditional knockout mouse lacking the conserved exons 11 and 12 of Talpid3. At early postnatal stages, the Talpid3 mutants exhibit a reduction in proliferation in the dentate gyrus and a disrupted glial scaffold. The occurrence of mis-localized progenitors in the granule cell layer suggests a role for the disrupted glial scaffold in cell migration resulting in defective subpial neurogenic zone-to-hilar transition. Neurospheres derived from the hippocampus of Talpid3fl/flUbcCre mouse, in which Talpid3 was conditionally deleted, lacked primary cilia and were smaller in size. In addition, neurosphere cells showed a disrupted actin cytoskeleton and defective migration. Our findings suggest a link between the hippocampal defects and the learning/memory deficits seen in JS patients. |
