Mammary gland development pathway - Embryonic development (Stage 1 of 4) (WP2813)

The mammary gland development can be subdivided into four stages of development: (1) embryonic development, (2) puberty, (3) pregnancy and lactation and (4) involution. In the embryonic development, a pair of mammary lines (ectoderm) arises, which gives origin to a pair of placodes. Then, each placode penetrates the underlying mesoderm. This results in the formation of the primary mammary gland [http://www.ncbi.nlm.nih.gov/pubmed/14668814 3]. NRG3 is a signal for placode formation. Besides that, it influences cell fate: it binds to its receptor, ERBB4, and induces MYC, which decreases expression of the integrins ITGA6 and ITGB1. The result is a change in cell adhesion and proliferation and consequent exit from the stem cell compartment [http://www.ncbi.nlm.nih.gov/pubmed/17880691 1]. Another process that should be highlighted in the embryonic development is the epithelial to mesenchymal transition (EMT). ZEB2 is an EMT regulator. It represses many genes (eg. CCND1, SFRP1, MIR200A, MIR200B, MIR429, TERT, CDH1, CLDN4 and ALPL), and also upregulates mesenchymal markers [http://www.ncbi.nlm.nih.gov/pubmed/19424592 2]. CCND1 and SFRP1 are related to cell proliferation, and SFRP1 are also related to WNT signaling pathway. MIR200A, MIR200B and MIR429 are microRNAs. TERT is responsible for elongation of telomere ends. CDH1 and CLDN4 are associated with cell adhesion, and ALPL may play a role in skeletal mineralization. Many genes modulate ZEB2. Some of these are shown in the figure [http://www.ncbi.nlm.nih.gov/pubmed/19424592 2]. TGFB1, TNF and IL1 are cytokines and AKT1 plays a role in many processes like cell proliferation, survival and growth. Hedgehog signals upregulate ZEB2 via TGFB1 [http://www.ncbi.nlm.nih.gov/pubmed/19424592 2].

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