The vertebrate Planar Cell Polarity pathway regulates Convergent Extension and Hair Cell Polarization independently in the Cochlea Open Access

Abstract

Abstract

The vertebrate Planar Cell Polarity pathway regulates Convergent Extension and Hair
Cell Polarization independently in the Cochlea
By Maria Fernanda Chacon Heszele
The planar cell polarity (PCP) signaling pathway consists of conserved
PCP and ciliary genes and is required for the apparent convergent extension
(CE) and coordinated cell polarization of the sensory hair cells in the mammalian
cochlea. However, it is unknown whether the PCP pathway regulates these two
diverse morphogenesis processes through the same molecular mechanism. We
found that the sensory epithelium in the mouse cochlea undergoes dramatic
changes in cell geometry and cellular boundary remodeling during CE.
Furthermore, this cellular morphogenesis is accompanied by dynamic expression
of adhesion components N-cadherin and E-cadherin, implying a role for cellular
adhesion molecules in CE. Supporting this idea, a conditional knockdown mouse
model of a component of adherens junctions, p120-catenin, shows altered or
diminished expression of N-and E-cadherins in the cochlea and phenocopies the
defects in cochlear extension observed in PCP and ciliary mutants. Interestingly,
the p120 knockout mice do not display defects in cell polarization, indicating a
specific role for p120 in CE but not hair cell polarization. Conversely, two mouse
models of the Usher syndrome, the most common genetic cause of human
deafness, show defects in cell polarization but no defects in cochlear CE. These
results indicate that the PCP signaling pathway regulates cell polarization and
CE of the cochlea independently via distinct molecular mechanisms. The
cochlear CE is driven by a p120-dependent mechanism while hair cell
polarization is regulated by a machinery involving Usher genes.

The vertebrate Planar Cell Polarity pathway regulates Convergent Extension and Hair
Cell Polarization independently in the Cochlea
By
Maria Fernanda Chacon Heszele
B.S./B.A., East Carolina University, 2004
Advisor: Ping Chen, Ph.D.
A dissertation submitted to the Faculty of the
James T. Laney School of Graduate Studies of Emory University
in partial fulfillment of the requirements for the degree of
Doctor of Philosophy
Graduate Division of Biological and Biomedical Sciences
Biochemistry, Cell, and Developmental Biology
2011

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School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Biochemistry, Cell & Developmental Biology
Degree	PhD
Submission	Dissertation
Language	English
Research Field	Biology, Cell
Keyword	Inner Ear Planar Cell Polarity Usher Syndrome Cell Adhesion Hair Cell Polarity Development
Committee Chair / Thesis Advisor	Chen, Ping Helen, Emory University
Committee Members	Kowalczyk, Andrew, Emory University Sale, Winfield S, Emory University Ono, Shoichiro, Emory University Caspary, Tamara, Emory University Faundez, Victor, Emory University

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