Ectodysplasin regulates hormone-independent mammary ductal morphogenesis via NF-kappa B
| Autor: | Ingrid Fliniaux, Pascal Schneider, Laura Ahtiainen, Maria Voutilainen, Ruth Schmidt-Ullrich, Sylvie Lefebvre, Marja Murtoniemi, Päivi H. Lindfors, Marja L. Mikkola, Elisa Rysti |
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| Rok vydání: | 2012 |
| Předmět: |
Male
EGF Family of Proteins medicine.medical_specialty Transcription Genetic Mammary gland Morphogenesis Embryonic Development Apoptosis Mice Transgenic Biology Ligands Amphiregulin Epithelium Mice 03 medical and health sciences Mammary Glands Animal 0302 clinical medicine Epidermal growth factor Internal medicine medicine Animals Cell Proliferation Glycoproteins 030304 developmental biology 0303 health sciences Multidisciplinary Epidermal Growth Factor Cell growth NF-kappa B Parathyroid Hormone-Related Protein Epigen Biological Sciences Ectodysplasins Hormones Cell biology Wnt Proteins medicine.anatomical_structure Endocrinology 030220 oncology & carcinogenesis Androgens Intercellular Signaling Peptides and Proteins Female Signal transduction |
| Zdroj: | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 15, pp. 5744-5749 |
| DOI: | 10.1073/pnas.1110627109 |
| Popis: | Ductal growth of the mammary gland occurs in two distinct stages. The first round of branching morphogenesis occurs during embryogenesis, and the second round commences at the onset of puberty. Currently, relatively little is known about the genetic networks that control the initial phases of ductal expansion, which, unlike pubertal development, proceeds independent of hormonal input in female mice. Here we identify NF-κB downstream of the TNF-like ligand ectodysplasin (Eda) as a unique regulator of embryonic and prepubertal ductal morphogenesis. Loss of Eda, or inhibition of NF-κB, led to smaller ductal trees with fewer branches. On the other hand, overexpression of Eda caused a dramatic NF-κB–dependent phenotype in both female and male mice characterized by precocious and highly increased ductal growth and branching that correlated with enhanced cell proliferation. We have identified several putative transcriptional target genes of Eda/NF-κB, including PTHrP , Wnt10a , and Wnt10b , as well as Egf family ligands a mphiregulin and epigen . We developed a mammary bud culture system that allowed us to manipulate mammary development ex vivo and found that recombinant PTHrP, Wnt3A, and Egf family ligands stimulate embryonic branching morphogenesis, suggesting that these pathways may cooperatively mediate the effects of Eda. |
| Databáze: | OpenAIRE |
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