Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptomic Analysis of Embryonic Mammary Cells

ABSTRACT: The mammary primordium represents the earliest evidence of commitment to the mammary lineage. The primordium forms via inductive tissue interactions between its constitutive tissues, the mesenchyme and epithelium. Here, we describe an analysis of the transcriptome of the mammary bud epithelium and its associated mesenchyme, two distinct cellular compartments that comprise the mammary primordium. Using network analysis, we found candidate mediators of mammary cell fate, differentiation and progenitor cell function that signal from mammary lineage inception during embryogenesis through postnatal development. Genetic features of mammary primordial cells overlapping with human breast progenitor cells identified potential regulators of key progenitor cell functions conserved across species. These results provide new insights into genetic regulatory mechanisms of mammary and in particular novel regulators of stromal-epithelial communications.

ORGANISM(S): Mus musculus

SUBMITTER: Alan Mackay

PROVIDER: E-TABM-1099 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment.

Wansbury Olivia O Mackay Alan A Kogata Naoko N Mitsopoulos Costas C Kendrick Howard H Davidson Kathryn K Ruhrberg Christiana C Reis-Filho Jorge S JS Smalley Matthew J MJ Zvelebil Marketa M Howard Beatrice A BA

Breast cancer research : BCR 20110811 4

<h4>Introduction</h4>The mammary primordium forms during embryogenesis as a result of inductive interactions between its constitutive tissues, the mesenchyme and epithelium, and represents the earliest evidence of commitment to the mammary lineage. Previous studies of embryonic mouse mammary epithelium indicated that, by mid-gestation, these cells are determined to a mammary cell fate and that a stem cell population has been delimited. Mammary mesenchyme can induce mammary development from simpl ...[more]

PMID: 21834968

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Project description:Previous studies have suggested that Bmp4 is a key Msx1-dependent mesenchymal odontogenic signal for driving tooth morphogenesis through the bud-to-cap transition. Whereas the bud stage tooth developmental arrest in Msx1-/- mutant mice was accompanied by reduction in mesenchymal Bmp4 mRNA expression, we show that depleting functional Bmp4 mRNAs in the tooth mesenchyme, through neural crest-specific gene inactivation in Bmp4f/f;Wnt1Cre mice, caused mandibular molar developmental arrest at the bud stage but allowed maxillary molars and incisors to develop to mineralized teeth. We show that the Wnt inhibitors Dkk2 and Wif1 were much more abundantly expressed in the mandibular than maxillary molar mesenchyme in wildtype embryos and that Dkk2 expression was significantly unregulated in the tooth mesenchyme in Bmp4f/f;Wnt1Cre embryos. In addition, expression of Osr2, which encodes a zinc finger protein that antagonizes Msx1-mediated activation of odontogenic mesenchyme, is significantly upregulated in the molar mesenchyme in Bmp4f/f;Wnt1Cre embryos. Msx1 heterozygosity enhanced maxillary molar developmental defects whereas Osr2 heterozygosity rescued mandibular first molar morphogenesis in Bmp4f/f;Wnt1Cre mice. Moreover, in contrast to complete lack of supernumerary tooth initiation in Msx1-/-Osr2-/- mutant mice, Osr2-/-Bmp4f/f;Wnt1Cre compound mutant mice exhibit formation and subsequent arrest of supernumerary tooth germs that correlated with down regulation of Msx1 expression in the tooth mesenchyme. Taken together, our data indicate that, while reduction in mesenchymal Bmp4 expression alone could not account for the tooth bud arrest phenotype in Msx1-/- mutant mice, Bmp4 signaling synergizes with Msx1 and antagonizes Osr2 to activate mesenchymal odontogenic activity to drive tooth morphogenesis and sequential tooth formation. E13.5 mouse embryos tooth germs were microdissected by laser capture microdissection (LCM), and the mandibular molar and maxillary molar were separated. 3 pairs of control and mutant samples were pooled for the RNA extraction.

Dataset Information

Transcriptomic Analysis of Embryonic Mammary Cells

Publications

Transcriptome analysis of embryonic mammary cells reveals insights into mammary lineage establishment.

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