Intraepithelial paracrine Hedgehog signaling induces the expansion of ciliated cells that express diverse progenitor cell markers in the basal epithelium of the mouse mammary gland

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dc.contributor.author García-Zaragoza, Elena
dc.contributor.author Pérez-Tavarez, Raquel
dc.contributor.author Ballester, Alicia
dc.contributor.author Lafarga, Vanesa
dc.contributor.author Jiménez-Reinoso, Anaïs
dc.contributor.author Ramírez, Ángel
dc.contributor.author Murillas, Rodolfo
dc.contributor.author Gallego, Marta I.
dc.date.accessioned 2014-06-16T11:32:33Z
dc.date.available 2014-06-16T11:32:33Z
dc.date.issued 2012-12-01
dc.identifier.bibliographicCitation Developmental biology, Vol. 372, nº 1 (2012), pp. 28-44
dc.identifier.uri http://hdl.handle.net/10016/19001
dc.description.abstract The Hedgehog signaling pathway regulates embryo patterning and progenitor cell homeostasis in adult tissues, including epidermal appendages. A role for the Hh pathway in mammary biology and breast cancer has also been suggested. The aim of this study was to analyze Hh signaling in the mouse mammary gland through the generation of transgenic mice that express Sonic Hedgehog (Shh) under the control of the mammary-specific WAP promoter (WAP-Shh mice). To identify mammary cells capable of activating the Hh pathway we bred WAP-Shh mice to Ptch1-lacZ knock-in mice, in which the expression of a nuclear-targeted β-galactosidase reporter protein (β-gal) is driven by the endogenous Patched 1 gene regulatory region. After two cycles of induction of transgenic Shh expression, we detected areas of X-gal reactivity. Immunohistochemical analysis showed nuclear β-gal staining in clusters of mammary cells in WAP-Shh/Ptch1-lacZ bitransgenic mice. These were epithelial cells present in a basal location of displastic ducts and alveoli, adjacent to Shh-expressing luminal cells, and overexpressed epithelial basal markers keratin 5, 14 and 17 and transcription factor p63. Absence of smooth muscle actin expression and a cuboidal morphology differentiated Hh-responding cells from flat-shaped mature myoepithelial cells. Groups of cells expressing stem cell markers integrin β3 and keratins 6 and 15 were also detected within Hh-responding areas. In addition, we found that Hh-responding cells in the mammary glands of WAP-Shh/Ptch1-lacZ mice were ciliated and exhibited a low proliferation rate. Our data show the paracrine nature of hedgehog signaling in the epithelial compartment of the mouse mammary gland, where a subset of basal cells that express mammary progenitor cell markers and exhibit primary cilia is expanded in response to secretory epithelium-derived Shh.
dc.description.sponsorship This work was supported by MCINN Grant no. SAF2006 03244, Fundación Marcelino Botín and Federación Española Cáncer de Mama (FECMA).
dc.format.extent 17
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.rights © 2012 Elsevier Inc.
dc.subject.other Mouse mammary gland; Hedgehog; Paracrine; Intraepithelial; Primary cilia; Progenitor cell; Ptch1
dc.title Intraepithelial paracrine Hedgehog signaling induces the expansion of ciliated cells that express diverse progenitor cell markers in the basal epithelium of the mouse mammary gland
dc.type article
dc.relation.publisherversion http://dx.doi.org/10.1016/j.ydbio.2012.09.005
dc.subject.eciencia Medicina
dc.identifier.doi 10.1016/j.ydbio.2012.09.005
dc.rights.accessRights openAccess
dc.relation.projectID Comunidad de Madrid. S2010/BMD-2420/CELLCAM
dc.type.version acceptedVersion
dc.identifier.publicationfirstpage 28
dc.identifier.publicationissue 1
dc.identifier.publicationlastpage 44
dc.identifier.publicationtitle Developmental biology
dc.identifier.publicationvolume 372
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