Search bioRxiv⌕ Search

Biology subjects

Walsh, G. S.

Publications and source records attributed to Walsh, G. S..

2 recordsLinked to original sources

Cadherins regulate nuclear topography and function of developing ocular motor circuitry

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.

developmental biology↗

Loss of Nance-Horan Syndrome b (nhsb) prevents expansion growth of retinal progenitor cells by selective up-regulation of Δ113p53

The regulation of cell cycle progression and differentiation in retinal progenitor cells is a fundamental feature controlling organ size of the eye in vertebrates. Nance-Horan Syndrome (NHS) is a rare X-linked disorder caused by mutations in the NHS gene. Dysmorphic features of NHS include severe congenital cataracts, micropthalmia, facial dysmorphisms, and visual impairment. In this study we report an evolutionarily conserved role for NHS in vertebrate retinogenesis. Loss of function of nhs leads to small eye size in both zebrafish and Xenopus tropicalis, marked by reduced proliferation but not cell death. Transcriptome analysis of nhs morphant zebrafish eyes revealed a marked upregulation in{Delta} 113p53, an isoform of p53, concomitant with a selective upregulation of p53 responsive genes that inhibit cell cycle progression but not apoptosis. Our data supports a model where Nhs is a negative regulator of{Delta} 113p53 expression and exerts its function through regulation of the p53 pathway to promote expansive growth of retinal progenitor cells prior to differentiation.

developmental biology↗