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Publication : Functional analysis of ectodermal β-catenin during external genitalia formation.

First Author  Mazahery AR Year  2013
Journal  Congenit Anom (Kyoto) Volume  53
Issue  1 Pages  34-41
PubMed ID  23480356 Mgi Jnum  J:194034
Mgi Id  MGI:5470180 Doi  10.1111/cga.12001
Citation  Mazahery AR, et al. (2013) Functional analysis of ectodermal beta-catenin during external genitalia formation. Congenit Anom (Kyoto) 53(1):34-41
abstractText  beta-catenin is a molecule belonging to the armadillo family of proteins that is a crucial core-component of cellular adherens junctions, and a component of the canonical Wnt-signaling pathway. We attempted to analyze the functional significance of ectodermal-derived beta-catenin during the development of the mouse genital tubercle, a mammalian anlage of the external genitalia. For this purpose, the conditional loss of function mouse mutant Wnt7a-Cre;beta-cat was utilized. Loss of ectodermal beta-catenin leads to the formation of urethral cleft during preputial uprising. Although expression of E-cadherin was retained in the genital tubercle ectoderm of mutants, probably through plakoglobin compensatory expression, expression of other crucial adherens junction components such as alpha-catenin and F-actin in the cell-cell border were distinctly reduced. We also showed that beta-catenin is necessary for the expression of its transcriptional downstream target Lef-1 which was localized in the basal layer of the preputial ectoderm, excluding the midventral region at E15.5. Such specialized region was observed to possess cytoplasmic beta-catenin expression at this stage. Coincidentally, mitotically active cells were also found in the basal layer of the preputial ectoderm excluding the midventral region. In mutant genital tubercle, cell proliferation in the preputial ectoderm was decreased. Taken together, we suggest that ectodermal beta-catenin is necessary not only to maintain adherens junction integrity, but also to regulate cell proliferation possibly through Lef-1 functions. Thus, beta-catenin is shown to perform dual functions, initially as an adhesion molecule and later on as a possible transcription factor.
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