Abstract
Purpose:
We previously showed that Mak is required for ciliary length regulation in retinal photoreceptor cells. Recent reports showed that mutations in human MAK cause retinitis pigmentosa. By contrast to cell type-specific expression of Mak, another murine ortholog of Chlamydomonas LF4, Intestinal Cell Kinase (ICK), shows ubiquitous expression including in the developing CNS. However, the exact biological functions of ICK have not yet been elucidated.
Methods:
We generated and analyzed retina- or brain-specific ICK-deficient mutant mice as well as conventional ICK-deficient mutant mice.
Results:
In ICK-null mutant mice, we observed some phenotypes of defective Hh signaling including polydactyly, shortened leg bones, and developmental defects of the cerebellum, hippocampus and retina. At the cellular level, we found that ICK is essential for ciliogenesis at least in retinal and neural progenitor cells and MEFs.
Conclusions:
Our results show that ICK controls protein transport at the ciliary tip and plays an essential role in ciliogenesis in retinal and neuronal progenitors but not in mature neurons, proposing a role for ICK in the regulation of IFT.
Keywords: 721 stem cells •
654 proliferation •
698 retinal development