| First Author | Waas B | Year | 2024 |
| Journal | Sci Adv | Volume | 10 |
| Issue | 17 | Pages | eade1650 |
| PubMed ID | 38669326 | Mgi Jnum | J:363340 |
| Mgi Id | MGI:7624973 | Doi | 10.1126/sciadv.ade1650 |
| Citation | Waas B, et al. (2024) Dual and opposing roles for the kinesin-2 motor, KIF17, in Hedgehog-dependent cerebellar development. Sci Adv 10(17):eade1650 |
| abstractText | While the kinesin-2 motors KIF3A and KIF3B have essential roles in ciliogenesis and Hedgehog (HH) signal transduction, potential role(s) for another kinesin-2 motor, KIF17, in HH signaling have yet to be explored. Here, we investigated the contribution of KIF17 to HH-dependent cerebellar development, where Kif17 is expressed in both HH-producing Purkinje cells and HH-responding cerebellar granule neuron progenitors (CGNPs). Germline Kif17 deletion in mice results in cerebellar hypoplasia due to reduced CGNP proliferation, a consequence of decreased HH pathway activity mediated through decreased Sonic HH (SHH) protein. Notably, Purkinje cell-specific Kif17 deletion partially phenocopies Kif17 germline mutants. Unexpectedly, CGNP-specific Kif17 deletion results in the opposite phenotype-increased CGNP proliferation and HH target gene expression due to altered GLI transcription factor processing. Together, these data identify KIF17 as a key regulator of HH-dependent cerebellar development, with dual and opposing roles in HH-producing Purkinje cells and HH-responding CGNPs. |
