Abstract
The Notch signaling pathway controls differentiation of hair cells and supporting cells in the vertebrate inner ear. Here, we have investigated whether Numb, a known regulator of Notch activity in Drosophila, is involved in this process in the embryonic chick. The chicken homolog of Numb is expressed throughout the otocyst at early stages of development and is concentrated at the basal pole of the cells. It is asymmetrically allocated at some cell divisions, as in Drosophila, suggesting that it could act as a determinant inherited by one of the two daughter cells and favoring adoption of a hair-cell fate. To test the implication of Numb in hair cell fate decisions and the regulation of Notch signaling, we used different methods to overexpress Numb at different stages of inner ear development. We found that sustained or late Numb overexpression does not promote hair cell differentiation, and Numb does not prevent the reception of Notch signaling. Surprisingly, none of the Numb-overexpressing cells differentiated into hair cells, suggesting that high levels of Numb protein could interfere with intracellular processes essential for hair cell survival. However, when Numb was overexpressed early and more transiently during ear development, no effect on hair cell formation was seen. These results suggest that in the inner ear at least, Numb does not significantly repress Notch activity and that its asymmetric distribution in dividing precursor cells does not govern the choice between hair cell and supporting cell fates.
Highlights
In many tissues, the Notch pathway mediates lateral inhibition and thereby governs cell diversification: cells expressing high levels of Notch ligands activate Notch in neighboring cells and in this way force them to adopt a different fate
We found that cleavage planes were quite variable: some were perpendicular to the plane of the epithelium (“vertical”), producing two cells that lay side by side in the epithelium; others were tilted such that a division produced one cell more apically and one cell more basally (Figure 1B)
Numb was identified in Drosophila as a critical regulator of Notch-dependent cell fate decisions during neurogenesis, acting as cell-intrinsic inhibitor of Notch activity during lateral inhibition
Summary
The Notch pathway mediates lateral inhibition and thereby governs cell diversification: cells expressing high levels of Notch ligands activate Notch in neighboring cells and in this way force them to adopt a different fate This process has been well studied in the developing mechanosensory bristles of Drosophila, and parallels between these insect sensillae and the mechanosensory epithelia of the vertebrate inner ear have guided our understanding of vertebrate ear development, and in particular of the role of Notch signaling in this process (Adam et al, 1998; Eddison et al, 2000). We focus on one of these modulators, Numb, and examine its role in the development of the sensory patches in the vertebrate inner ear Does it act there, as it does in the insect bristle, to control choices of cell fate?
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
