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Mammary gland morphogenesis depends on a tight balance between cell proliferation, differentiation and apoptosis, to create a defined functional hierarchy within the epithelia. The limited availability of stem cell/progenitor markers has made it challenging to decipher lineage relationships. Here, we identify a rare subset of luminal progenitors that express the zinc finger transcriptional repressor Blimp1, and demonstrate that this subset of highly clonogenic luminal progenitors is required for mammary gland development. Conditional inactivation experiments using K14-Cre and WAPi-Cre deleter strains revealed essential functions at multiple developmental stages. Thus, Blimp1 regulates proliferation, apoptosis and alveolar cell maturation during puberty and pregnancy. Loss of Blimp1 disrupts epithelial architecture and lumen formation both in vivo and in three-dimensional (3D) primary cell cultures. Collectively, these results demonstrate that Blimp1 is required to maintain a highly proliferative luminal subset necessary for mammary gland development and homeostasis.

Original publication

DOI

10.1242/dev.136358

Type

Journal article

Journal

Development

Publication Date

15/05/2016

Volume

143

Pages

1663 - 1673

Keywords

3D culture, Blimp1, Lumen formation, Luminal progenitors, Mammary gland morphogenesis, Mouse, Polarity, Prdm1, Transcriptional repressor, Animals, Cell Compartmentation, Cell Differentiation, Cell Polarity, Cells, Cultured, Clone Cells, Epithelial Cells, Female, Gene Expression Regulation, Developmental, Hormones, Lactation, Mammary Glands, Animal, Mice, Inbred C57BL, Morphogenesis, Positive Regulatory Domain I-Binding Factor 1, Pregnancy, Repressor Proteins, Stem Cells, Steroids, Transcription Factors, Up-Regulation