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First published online 18 March 2009
doi: 10.1242/dev.023994

Development 136, 1423-1432 (2009)
Published by The Company of Biologists 2009
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Ptch1 is required locally for mammary gland morphogenesis and systemically for ductal elongation

Ricardo C. Moraes1, Hong Chang2, Nikesha Harrington1, John D. Landua1, Jonathan T. Prigge1, Timothy F. Lane3, Brandon J. Wainwright4, Paul A. Hamel2 and Michael T. Lewis1,*

1 Lester and Sue Smith Breast Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
2 Department of Laboratory Medicine and Pathobiology, Faculty of Medicine,1 King's College Circle, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
3 UCLÁs Jonsson Comprehensive Cancer Center, 8-684 Factor Building, Box 951781, Los Angeles, CA 90095, USA.
4 Institute for Molecular Bioscience, The University of Queensland, 306 Carmody Road, Brisbane, Queensland 4072, Australia.

* Author for correspondence (e-mail: mtlewis{at}bcm.edu)

Accepted 19 February 2009

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.

Key words: Hedgehog, SMO, Ductal morphogenesis, Hyperplasia, Pituitary isograft, Tissue interaction, Mouse


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© The Company of Biologists Ltd 2009