Cadherins regulate nuclear topography and function of developing ocular motor circuitry

Author:

Knüfer Athene1ORCID,Diana Giovanni1ORCID,Walsh Gregory S2,Clarke Jonathan DW1,Guthrie Sarah3ORCID

Affiliation:

1. Centre for Developmental Neurobiology, King’s College London, London, United Kingdom

2. Department of Biology, Virginia Commonwealth University, Richmond, United States

3. School of Life Sciences, University of Sussex, Brighton, United Kingdom

Abstract

In the vertebrate central nervous system, groups of functionally related neurons, including cranial motor neurons of the brainstem, are frequently organised as nuclei. The molecular mechanisms governing the emergence of nuclear topography and circuit function are poorly understood. Here we investigate the role of cadherin-mediated adhesion in the development of zebrafish ocular motor (sub)nuclei. We find that developing ocular motor (sub)nuclei differentially express classical cadherins. Perturbing cadherin function in these neurons results in distinct defects in neuronal positioning, including scattering of dorsal cells and defective contralateral migration of ventral subnuclei. In addition, we show that cadherin-mediated interactions between adjacent subnuclei are critical for subnucleus position. We also find that disrupting cadherin adhesivity in dorsal oculomotor neurons impairs the larval optokinetic reflex, suggesting that neuronal clustering is important for co-ordinating circuit function. Our findings reveal that cadherins regulate distinct aspects of cranial motor neuron positioning and establish subnuclear topography and motor function.

Funder

Biotechnology and Biological Sciences Research Council

Company of Biologists

Wellcome Trust

Medical Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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