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J. Cell Biol.,
Volume 143, Number 7, December 28, 1998 2009-2022
Howard Hughes Medical Institute and Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago
Illinois 60637
Desmosomes first assemble in the E3.5
mouse trophectoderm, concomitant with establishment
of epithelial polarity and appearance of a blastocoel
cavity. Throughout development, they increase in size
and number and are especially abundant in epidermis
and heart muscle. Desmosomes mediate cell-cell adhesion through desmosomal cadherins, which differ from
classical cadherins in their attachments to intermediate
filaments (IFs), rather than actin filaments. Of the proteins implicated in making this IF connection, only desmoplakin (DP) is both exclusive to and ubiquitous
among desmosomes. To explore its function and importance to tissue integrity, we ablated the desmoplakin
gene. Homozygous
/
mutant embryos proceeded through implantation, but did not survive beyond E6.5.
Mutant embryos proceeded through implantation, but
did not survive beyond E6.5. Surprisingly, analysis of
these embryos revealed a critical role for desmoplakin
not only in anchoring IFs to desmosomes, but also in
desmosome assembly and/or stabilization. This finding not only unveiled a new function for desmoplakin, but
also provided the first opportunity to explore desmosome function during embryogenesis. While a blastocoel cavity formed and epithelial cell polarity was at
least partially established in the DP (
/
) embryos, the paucity of desmosomal cell-cell junctions severely affected the modeling of tissue architecture and shaping
of the early embryo.
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