ZFIN ID: ZDB-PUB-191102-9
Notch-Mediated Determination of Hair-Bundle Polarity in Mechanosensory Hair Cells of the Zebrafish Lateral Line
Jacobo, A., Dasgupta, A., Erzberger, A., Siletti, K., Hudspeth, A.J.
Date: 2019
Source: Current biology : CB   29(21): 3579-3587.e7 (Journal)
Registered Authors: Dasgupta, Agnik, Erzberger, Anna, Hudspeth, A.J. (Jim)
Keywords: Emx2, bistability, delta, lateral inhibition, neuromast, planar cell polarity
MeSH Terms:
  • Animals
  • Cell Differentiation/genetics*
  • Cell Polarity/genetics*
  • Hair Cells, Auditory/metabolism
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Lateral Line System/physiology*
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Receptor, Notch1/genetics*
  • Receptor, Notch1/metabolism
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 31668618 Full text @ Curr. Biol.
The development of mechanosensory epithelia, such as those of the auditory and vestibular systems, results in the precise orientation of mechanosensory hair cells. 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 a 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 an undiscovered polarity effector.