The vertebrate Planar Cell Polarity pathway regulates Convergent Extension and Hair Cell Polarization independently in the Cochlea 公开
Chacon Heszele, Maria Fernanda (2011)
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
Table of Contents
Table of Contents
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