Cadherins regulate nuclear topography and function of developing ocular motor circuitry
- King's College London, United Kingdom
- Virginia Commonwealth University, United States
- University of Sussex, 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.
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The data that support the findings in this study are available within the article and supporting files.
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Author details
Funding
Biotechnology and Biological Sciences Research Council (BB/J014567/1)
- Athene Knüfer
Company of Biologists (DEV-170218)
- Athene Knüfer
Wellcome Trust (102895/Z/13/Z)
- Jonathan DW Clarke
Medical Research Council (MR/L020742/2)
- Sarah Guthrie
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This work was approved by the local Animal Care and Use Committee (King's College London) and was carried out in accordance with the Animals (Experimental Procedures) Act, 1986, under licence from the United Kingdom Home Office (PPLs: 70/7753 and P70880F4C-Z001, PIL: I1D87502D).
Copyright
© 2020, Knüfer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cadherins regulate nuclear topography and function of developing ocular motor circuitry
eLife 9:e56725.
https://doi.org/10.7554/eLife.56725
