Investigating the Roles of the ciliary kinase CSNK2A1 in mediating Neural Tube Patterning During Neurogenesis — 90a — Gracie Hoffman, Ajuangatat Anyaak Chol, Elizabeth Menzel, and Abdelhalim Loukil

Primary cilia are microtubule-based organelles essential for signal transduction and  embryonic development. They regulate a variety of signaling pathways, including the Sonic  Hedgehog (SHH) pathway. Mutations in ciliary genes cause a wide spectrum of human diseases and syndromes, termed ciliopathies. We previously identified Casein kinase II alpha 1  (CSNK2A1) as a modulator of cilia trafficking and stability, acting as a negative regulator of the  SHH pathway in vitro. Our goal was to assess the requirement for this kinase to mediate SHH  during embryonic development. Therefore, we employed the patterning of the ventral  progenitors of the neural tube as a readout of SHH signaling in vivo. We hypothesized that  Csnk2a1 -/- embryos present an expansion of the ventral progenitors within the neural tubes. 

We found that Csnk2a1-/- mutations are lethal by embryonic stage E11.5. They were  underdeveloped and present a partially open neural tube. We then conducted timed matings between Csnk2a1 +/- mice and collected E10.5 embryos that were dissected and split into head,  thoracic, and caudal sections. Embryos were sectioned and stained with markers for ventral and  dorsal progenitors, OLIG2 and PAX6. Domain lengths were then normalized to total neural tube  length producing ratios that were statistically compared between mutants and controls. A  significant expansion of the PAX6 domain was observed in the thoracic and caudal sections of  the Csnk2a1 -/- embryo; however, the OLIG2 domain was found to be consistent between  mutant and controls. The expansion of the PAX6 domain suggests that there is a reduction in SHH activity in Csnk2a1-/- mutant embryos. We plan to expand this study by staining additional  neural progenitors for the SHH and WNT pathways. Understanding the roles of CSNK2A1 in  neural patterning and cell fate will expand our knowledge of how primary cilia modulate early  processes of brain development.

Sanford Research
Abdelhalim Loukil