Differential requirements for shh in mammary tissue and hair follicle morphogenesis.
Sonic Hedgehog (Shh) is a secreted morphogen that directs patterning and cellular differentiation through binding to its receptor Patched (Ptc). It is required for the development of skin-derived organs, such as hair, whiskers, and teeth. The mammary gland is a skin-derived organ that develops mainly during adult life in which Shh is expressed from puberty to lactation. We have investigated the role of Shh in mammary gland morphogenesis and differentiation by two transplantation approaches. Since Shh-null fetuses die at late embryogenesis, we transplanted Shh-null mammary anlagen into cleared fat pads and under the renal capsule of wild type host mice. Pregnancy-mediated functional differentiation of Shh-null mammary epithelium was indistinguishable from wild type transplants, while hair follicles derived from cotransplanted skin only developed in wild type transplants. Transplants of Ihh-null anlagen also developed normally. To assess the molecular consequences of Shh deletion in mammary tissue, we compared mRNA levels of patched 1, a target gene of Hedgehog signaling, in Shh-null and wild type mammary epithelial transplants. No reduction of Ptc1 transcripts was observed in Shh-null mammary tissues. Our results demonstrate that neither Shh nor Ihh is required for mammary gland morphogenesis and functional differentiation, suggesting that the two members of the Hedgehog family may have redundant function in activating the Ptc1 signaling pathway during mammary gland development.
Gallego
Marta I
MI
Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland 20892, USA.
Beachy
Philip A
PA
Hennighausen
Lothar
L
Robinson
Gertraud W
GW
D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D018859:Hair Follicle / Q000196:embryology / Q000378:metabolism* / Q000637:transplantation; D053823:Hedgehog Proteins; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D007668:Kidney; D008321:Mammary Glands, Animal / Q000196:embryology* / Q000378:metabolism* / Q000637:transplantation; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009024:Morphogenesis / Q000235:genetics; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D019737:Transplants
D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D015534:Trans-Activators