KIF3C Regulates Bergmann Glia Density and Patterning during Cerebellar Development

Abstract

Kinesin-2 motors have been demonstrated to regulate Hedgehog (HH) signaling, particularly within the developing cerebellum (Spassky et al., 2008; Waas et al., 2024). KIF3A/KIF3B are required for ciliogenesis in mice, and loss of this motor complex results in cerebellar hypoplasia due to lack of mitogenic response of HH-responsive cerebellar granule neural progenitors (CGNPs). Homodimeric KIF17 regulates HH-dependent CGNP proliferation through regulating levels of SHH and GLI3 but is not required for ciliogenesis in the developing cerebellum. Germline deletion of Kif3c has previously been reported to have no effect on embryonic development or gross cerebellar morphology in adult mice (Yang et al., 2001). Examination of these mice during neonatal development reveal cerebellar hypoplasia due to reduced CGNP proliferation in Kif3c mutant mice. While decreased CGNP proliferation is often associated with reduced Hedgehog (HH) signaling, we did not detect a change in the levels of HH signaling in Kif3c-/- cerebella. However, we observed Bergmann glia density and localization is altered in Kif3c mutants, a phenotype consistent with disrupted Notch signaling. Further, we detected reduced expression of Hes1 in Kif3c-/- cerebella. Altogether, these data demonstrate KIF3C is required for proper cerebellar development but in a HH-independent manner. HighlightsO_LIKif3c is widely expressed in developing cerebellum C_LIO_LIKIF3C regulates cerebellar size, but in a HH-independent manner C_LIO_LIKif3c-/- mice have increased BG density and abnormal spatial patterning C_LI