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

Moraes, R. C., Chang, H, Harrington, N, Landua, J. D., Prigge, J. T., Lane, T. F., Wainwright, B. J., Hamel, P. A. and Lewis, M. T. (2009) Ptch1 is required locally for mammary gland morphogenesis and systemically for ductal elongation. DEVELOPMENT, 136 9: 1423-1432. doi:10.1242/dev.023994

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Author Moraes, R. C.
Chang, H
Harrington, N
Landua, J. D.
Prigge, J. T.
Lane, T. F.
Wainwright, B. J.
Hamel, P. A.
Lewis, M. T.
Title Ptch1 is required locally for mammary gland morphogenesis and systemically for ductal elongation
Journal name DEVELOPMENT   Check publisher's open access policy
ISSN 0950-1991
Publication date 2009-05
Year available 2009
Sub-type Article (original research)
DOI 10.1242/dev.023994
Open Access Status File (Publisher version)
Volume 136
Issue 9
Start page 1423
End page 1432
Total pages 10
Editor Jim Smith
Place of publication Cambridge, England, U.K.
Publisher The Company of Biologists
Collection year 2010
Language eng
Subject C1
970106 Expanding Knowledge in the Biological Sciences
060403 Developmental Genetics (incl. Sex Determination)
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 (Ptch1mes), we found that Ptch1mes 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 Ptch1mes 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.
Keyword Hedgehog
CELL-CYCLE PROGRESSION
SMO
Ductal morphogenesis
Hyperplasia
Pituitary isograft
Tissue interaction
Mouse
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 18 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 03 Sep 2009, 08:22:17 EST by Mr Andrew Martlew on behalf of Institute for Molecular Bioscience