Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development
Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for the proper development of the embryonic mammary gland in mice. Using a combination of loss-of-function and gain-of-function models, we now report that PTHrP regul...
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| Vydané v: | Development (Cambridge) Ročník 128; číslo 4; s. 513 |
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| Hlavní autori: | , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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15.02.2001
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| ISSN: | 0950-1991 |
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| Abstract | Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for the proper development of the embryonic mammary gland in mice. Using a combination of loss-of-function and gain-of-function models, we now report that PTHrP regulates a series of cell fate decisions that are central to the survival and morphogenesis of the mammary epithelium and the formation of the nipple. PTHrP is made in the epithelial cells of the mammary bud and, during embryonic mammary development, it interacts with the surrounding mesenchymal cells to induce the formation of the dense mammary mesenchyme. In response, these mammary-specific mesenchymal cells support the maintenance of mammary epithelial cell fate, trigger epithelial morphogenesis and induce the overlying epidermis to form the nipple. In the absence of PTHrP signaling, the mammary epithelial cells revert to an epidermal fate, no mammary ducts are formed and the nipple does not form. In the presence of diffuse epidermal PTHrP signaling, the ventral dermis is transformed into mammary mesenchyme and the entire ventral epidermis becomes nipple skin. These alterations in cell fate require that PTHrP be expressed during development and they require the presence of the PTH/PTHrP receptor. Finally, PTHrP signaling regulates the epidermal and mesenchymal expression of LEF1 and ( )-catenin, suggesting that these changes in cell fate involve an interaction between the PTHrP and Wnt signaling pathways. |
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| AbstractList | Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for the proper development of the embryonic mammary gland in mice. Using a combination of loss-of-function and gain-of-function models, we now report that PTHrP regulates a series of cell fate decisions that are central to the survival and morphogenesis of the mammary epithelium and the formation of the nipple. PTHrP is made in the epithelial cells of the mammary bud and, during embryonic mammary development, it interacts with the surrounding mesenchymal cells to induce the formation of the dense mammary mesenchyme. In response, these mammary-specific mesenchymal cells support the maintenance of mammary epithelial cell fate, trigger epithelial morphogenesis and induce the overlying epidermis to form the nipple. In the absence of PTHrP signaling, the mammary epithelial cells revert to an epidermal fate, no mammary ducts are formed and the nipple does not form. In the presence of diffuse epidermal PTHrP signaling, the ventral dermis is transformed into mammary mesenchyme and the entire ventral epidermis becomes nipple skin. These alterations in cell fate require that PTHrP be expressed during development and they require the presence of the PTH/PTHrP receptor. Finally, PTHrP signaling regulates the epidermal and mesenchymal expression of LEF1 and ( )-catenin, suggesting that these changes in cell fate involve an interaction between the PTHrP and Wnt signaling pathways. Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for the proper development of the embryonic mammary gland in mice. Using a combination of loss-of-function and gain-of-function models, we now report that PTHrP regulates a series of cell fate decisions that are central to the survival and morphogenesis of the mammary epithelium and the formation of the nipple. PTHrP is made in the epithelial cells of the mammary bud and, during embryonic mammary development, it interacts with the surrounding mesenchymal cells to induce the formation of the dense mammary mesenchyme. In response, these mammary-specific mesenchymal cells support the maintenance of mammary epithelial cell fate, trigger epithelial morphogenesis and induce the overlying epidermis to form the nipple. In the absence of PTHrP signaling, the mammary epithelial cells revert to an epidermal fate, no mammary ducts are formed and the nipple does not form. In the presence of diffuse epidermal PTHrP signaling, the ventral dermis is transformed into mammary mesenchyme and the entire ventral epidermis becomes nipple skin. These alterations in cell fate require that PTHrP be expressed during development and they require the presence of the PTH/PTHrP receptor. Finally, PTHrP signaling regulates the epidermal and mesenchymal expression of LEF1 and ( )-catenin, suggesting that these changes in cell fate involve an interaction between the PTHrP and Wnt signaling pathways.Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for the proper development of the embryonic mammary gland in mice. Using a combination of loss-of-function and gain-of-function models, we now report that PTHrP regulates a series of cell fate decisions that are central to the survival and morphogenesis of the mammary epithelium and the formation of the nipple. PTHrP is made in the epithelial cells of the mammary bud and, during embryonic mammary development, it interacts with the surrounding mesenchymal cells to induce the formation of the dense mammary mesenchyme. In response, these mammary-specific mesenchymal cells support the maintenance of mammary epithelial cell fate, trigger epithelial morphogenesis and induce the overlying epidermis to form the nipple. In the absence of PTHrP signaling, the mammary epithelial cells revert to an epidermal fate, no mammary ducts are formed and the nipple does not form. In the presence of diffuse epidermal PTHrP signaling, the ventral dermis is transformed into mammary mesenchyme and the entire ventral epidermis becomes nipple skin. These alterations in cell fate require that PTHrP be expressed during development and they require the presence of the PTH/PTHrP receptor. Finally, PTHrP signaling regulates the epidermal and mesenchymal expression of LEF1 and ( )-catenin, suggesting that these changes in cell fate involve an interaction between the PTHrP and Wnt signaling pathways. |
| Author | Wysolmerski, J Dann, P Foley, J Rimm, D Philbrick, W Dreyer, B Dunbar, M Cosgrove, J Hong, J |
| Author_xml | – sequence: 1 givenname: J surname: Foley fullname: Foley, J organization: Medical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA – sequence: 2 givenname: P surname: Dann fullname: Dann, P – sequence: 3 givenname: J surname: Hong fullname: Hong, J – sequence: 4 givenname: J surname: Cosgrove fullname: Cosgrove, J – sequence: 5 givenname: B surname: Dreyer fullname: Dreyer, B – sequence: 6 givenname: D surname: Rimm fullname: Rimm, D – sequence: 7 givenname: M surname: Dunbar fullname: Dunbar, M – sequence: 8 givenname: W surname: Philbrick fullname: Philbrick, W – sequence: 9 givenname: J surname: Wysolmerski fullname: Wysolmerski, J |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/11171335$$D View this record in MEDLINE/PubMed |
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| Snippet | Prior reports have demonstrated that both parathyroid hormone-related protein (PTHrP) and the type I PTH/PTHrP receptor are necessary for the proper... |
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| SubjectTerms | Animals beta Catenin Cell Differentiation Cell Lineage Cytoskeletal Proteins - analysis DNA-Binding Proteins - analysis Epidermal Cells Epidermis - embryology Epithelial Cells - cytology Female Gene Expression Regulation, Developmental Histocytochemistry Lymphoid Enhancer-Binding Factor 1 Mammary Glands, Animal - cytology Mammary Glands, Animal - embryology Mice Mice, Knockout Mice, Transgenic Models, Biological Nipples - cytology Nipples - embryology Parathyroid Hormone-Related Protein Proteins - genetics Proteins - metabolism Receptor, Parathyroid Hormone, Type 1 Receptors, Parathyroid Hormone - genetics Receptors, Parathyroid Hormone - metabolism Signal Transduction Trans-Activators Transcription Factors - analysis Transgenes - genetics |
| Title | Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development |
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