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Publication : Ptch1 is required locally for mammary gland morphogenesis and systemically for ductal elongation.

First Author  Moraes RC Year  2009
Journal  Development Volume  136
Issue  9 Pages  1423-32
PubMed ID  19297414 Mgi Jnum  J:147994
Mgi Id  MGI:3843130 Doi  10.1242/dev.023994
Citation  Moraes RC, et al. (2009) Ptch1 is required locally for mammary gland morphogenesis and systemically for ductal elongation. Development 136(9):1423-32
abstractText  Systemic hormones and local growth factor-mediated tissue interactions are essential for mammary gland development. Using phenotypic and transplantation analyses of mice carrying the mesenchymal dysplasia (mes) allele of patched 1 (Ptch1(mes)), we found that Ptch1(mes) homozygosity led to either complete failure of gland development, failure of post-pubertal ductal elongation, or delayed growth with ductal dysplasia. All ductal phenotypes could be present in the same animal. Whole gland and epithelial fragment transplantation each yielded unique morphological defects indicating both epithelial and stromal functions for Ptch1. However, ductal elongation was rescued in all cases, suggesting an additional systemic function. Epithelial function was confirmed using a conditional null Ptch1 allele via MMTV-Cre-mediated disruption. In Ptch1(mes) homozygotes, failure of ductal elongation correlated with diminished estrogen and progesterone receptor expression, but could not be rescued by exogenous ovarian hormone treatment. By contrast, pituitary isografts were able to rescue the ductal elongation phenotype. Thus, Ptch1 functions in the mammary epithelium and stroma to regulate ductal morphogenesis, and in the pituitary to regulate ductal elongation and ovarian hormone responsiveness.
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