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PMID: 19297414 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Development (Cambridge, England) ·Vol. 136 ·No. 9 ·2009-05-00 ·Pages 1423-32

Moraes RC, Chang H, Harrington N, Landua JD, Prigge JT, Lane TF, Wainwright BJ, Hamel PA, Lewis MT

Abstract

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.

MeSH Terms
Animals Base Sequence Epithelium/metabolism Estrogens/pharmacology Female Gene Expression Regulation, Developmental Genes, Reporter/genetics Heterozygote Homozygote Humans Male Mammary Glands, Animal/abnormalities,drug effects,growth & development,metabolism Mammary Tumor Virus, Mouse/genetics Mice Mice, Transgenic Morphogenesis Mutation/genetics Patched Receptors Patched-1 Receptor Polymorphism, Genetic/genetics Progesterone/pharmacology Receptors, Cell Surface/genetics,metabolism Stromal Cells/metabolism
Chemicals
Estrogens PTCH1 protein, human Patched Receptors Patched-1 Receptor Ptch1 protein, mouse Receptors, Cell Surface Progesterone
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Moraes Ricardo C
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Chang Hong
Harrington Nikesha
Landua John D
Prigge Jonathan T
Lane Timothy F
Wainwright Brandon J
Hamel Paul A
Lewis Michael T
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Article Info
Journal
Development (Cambridge, England)
Abbr.
Development
ISSN
0950-1991
DOI
10.1242/dev.023994
Published
2009-05-00
Epub
2009-00-18
Pages
1423-32
Language
English
Region
England
NLM ID
8701744
PMCID
PMC2675781
Subset
IM
Grants
NCI NIH HHS · R01 CA127857 · United States
NCI NIH HHS · P01 CA030195 · United States
NCI NIH HHS · P01-CA30195 · United States
NICHD NIH HHS · P01 HD038129 · United States
NCI NIH HHS · R01-CA127857 · United States
External Links
PubMed source DOI: 10.1242/dev.023994 PMC Full Text View journal details
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