A Ciliopathy Gene CC2D2a is Required For Eye Development

Abstract

Purpose: : CC2D2a (Coiled-Coil & C2 Domain containing 2a) has been identified as one of the causal genes associated with ciliopathies like Joubert syndrome (JS) and Meckel-Gruber syndrome (MKS) in patients. Photoreceptor morphology and function require an intact connecting cilium. Hence, the goal of this project is to determine the role of CC2D2a in photoreceptor development and function.

Methods: : In order to test whether mutations of CC2D2a alone could cause JS- and MKS-like phenotypes, we sought to knock down its function in zebrafish. This was accomplished using anti-sense morpholinos (both translation-blocking and splice-blocking). A CC2D2a-KO mouse has been generated to further explore its role in cilia-related functions with a focus on photoreceptor development.

Results: : After injection with anti-sense CC2D2a morpholinos, zebrafish embryos showed dose-dependent defects. Notably, the eye is smaller than in control zebrafish, and appeared to be malformed. The morphant zebrafish also showed convergent extension (CE) defects. Additionally, CC2D2a MO-injected zebrafish are much smaller than those injected with control morpholinos. The characterization of CC2D2a-KO mouse is in progress.

Conclusions: : Our zebrafish data indicate that CC2D2a plays a role in primary cilia biogenesis and is required for photoreceptor development.

Keywords: retinal development