Evaluation of the role of Formin-2 in the devleopment and function of the posterior lateral line in zebrafish

Abstract

Interconnected neural circuits give rise to behavior. For the formation of these neural circuits, axonal guidance during development is essential. Axonal guidance requires the remodelling of the actin cytoskeleton that helps the neurons in reaching their respective targets to form neural circuits. Formin-2 (Fmn2) is an actin cytoskeleton remodelling protein. Zebrafish larvae have Fmn2 selectively enriched in the brain, spinal cord, and the retinal ganglionic cells. The knockdown of Fmn2 in zebrafish larvae results in balance defects. The larvae frequently fall on their sides and swim with reduced directionality while receiving tactile stimuli. Zebrafish have different organs for mediating balance and posture that are the lateral line, inner ear, axial muscles, pectoral fins, and the swim bladder. The lateral line helps in the orientation of the larvae towards water current that is essential for keeping balance in the water. The lateral line has a set of mechanosensory organs known as neuromasts that sense mechanical stimuli. The neuromasts are deposited along the trunk and the tail of the larvae by a migrating group of cells known as the primordium. The neuromasts are innervated by sensory neurons. The lateral line system has two branches the anterior lateral line and the posterior lateral line. The goal of the project is to investigate whether any defect in the posterior lateral line contributes to the balance defect observed by Fmn2 knockdown. Our results show that Fmn2 is not involved in mediating the migration of the posterior lateral line primordium and the deposition of the neuromasts. Preliminary data show that the functionality of the neuromasts may get affected by the knockdown of Fmn2. From our study, the overall development and the functionality of the lateral line does not seem to get affected by Fmn2 knockdown. The development and functionality of the lateral line neurons also has to be studied further to examine if the mechanical stimuli is received by the sensory neurons of the lateral line. In order to observe the morphology of the lateral line neurons, we cloned the transgenic constructs HuC:mVenus-CAAX and HuC:mKOFP2-CAAX using gateway cloning. If Fmn2 knockdown does not affect the lateral line balance circuit other balance related organs in zebrafish larvae have to be studied in future.