DOI: 10.1101/480798Nov 28, 2018Paper

Notch-Mediated Polarity Decisions in Mechanosensory Hair Cells

BioRxiv : the Preprint Server for Biology
Adrian JacoboA J Hudspeth

Abstract

The development of mechanosensory epithelia, such as those of the auditory and vestibular systems, results in the precise orientation of mechanosensory hair cells and consequently directional sensitivity. After division of a precursor cell in the zebrafish's lateral line, the daughter hair cells differentiate with opposite mechanical sensitivity. Through a combination of theoretical and experimental approaches, we show that Notch1a-mediated lateral inhibition produces a bistable switch that reliably gives rise to cell pairs of opposite polarity. Using our mathematical model of the process, we predict the outcome of several genetic and chemical alterations to the system, which we then confirm experimentally. We show that Notch1a downregulates the expression of Emx2, a transcription factor known to be involved in polarity specification, and acts in parallel with the planar-cell-polarity system to determine the orientation of hair bundles. By analyzing the effect of simultaneous genetic perturbations to Notch1a and Emx2 we infer that the gene-regulatory network determining cell polarity includes undiscovered polarity effectors.

Related Concepts

Down-Regulation
Hair
Auditory Hair Cell
Stem Cells
Transcription Factor
Vestibule
Zebrafish
Cell Polarity
Cell Line, Tumor
Lateral

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