Mechanisms of Visual Circuit Assembly in Zebrafish

Abstract

One of the most outstanding and unique features of the central nervous system is the complexity underlying its neural circuit assembly. Development of the vertebrate visual system is dependent on the correct morphological and functional connectivity between synaptic partners. Cell adhesion molecules expressed in specific cell types are known not only to mediate the connections between pre- and postsynaptic partners but to maintain them after they have been made. However, the full extent of the mechanism responsible for neuronal wiring within the retina and between the retina and its retinorecipient nuclei in the brain is still far from complete. During my PhD, I started bridging this knowledge gap by investigating the role of the synaptic adhesion protein, teneurin-4, in shaping the morphological and functional connectivity in the vertebrate visual system. Making use of a zebrafish CRISPR knockout combined with a wide range of techniques, including but not limited to, single cell labelling, in vivo functional and structural imaging we were able to assess the role of teneurin-4 (tenm4) in the assembly of defined retinal circuits, specifically in the correct morphological development of retinal ganglion cell (RGC) axonal arbors and tectal cell (TC) dendritic arbors in the tectum. Furthermore, we detect an aberrant distribution of the presynaptic protein synaptophysin in RGC axonal arbors, as well as of the postsynaptic density protein PSD-95 in TC dendritic arbors - suggesting a role for tenm4 in synaptogenesis and/or synaptic organisation. Mutations in human TENM4 have been linked to bipolar disorder. Our findings therefore have the potential to lead to a better understanding of the aetiology of this disorder, as well as the general mechanisms involved in the creation of functional synaptic networks in healthy state.

Date of Award	1 Dec 2021
Original language	English
Awarding Institution	King's College London
Supervisor	Robert Hindges (Supervisor) & Martin Meyer (Supervisor)