Molecular Mechanisms of Cerebellar Circuit Formation - Contribution of Genes Associated with Ciliopathies

Research project

Neural circuits are the basis for learning and memory. The establishment of proper neural circuits depends on signaling pathways, some of which are controlled by primary cilia, organelles that serve as antennae of cells. We aim to elucidate the role of primary cilia in the establishment of neuronal circuits, with a special focus on cerebellar circuits in the zebrafish and the chick embryo.

We have found that cerebellar neurons of zebrafish mutants for the ciliopathy genes cc2d2a and talpid3 have fewer primary cilia that are positive for the ciliary GTPase Arl13b at larval stages compared to wild type controls. A detailed analysis of cerebellar axon tract morphology is ongoing.

The mutant larvae have a dysregulated expression of voltage-gated ion channels that are important for neuronal function. We are using transgenic zebrafish lines expressing neuron-specific genetically encoded calcium indicators in combination with behavioural assays to analyse neuronal function in cc2d2a mutants.

Since this project relies on two complementary model systems, the zebrafish and the chick embryo, and on a combination of functional, morphological and advanced imaging techniques including mesoSPIM, it generates synergies between the strengths of two groups.

Research groups

Principal investigators: Ruxandra Bachmann, Esther Stoeckli

PhD student: Alexandra Noble

Platforms: HDDA

Publications

Noble A, Masek M, Hofmann C, Cuoco A, Rusterholz T, Özkoc H, Greter N, Vladimirov N,   Kollmorgen S, Stoeckli E, Bachmann-Gagescu R (2024)
Shared and unique consequences of Joubert-gene loss-of-function on the zebrafish central nervous systembioRxiv

Underlined: AdaBD researchers