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

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231131111113111111131Cell junctionMesenchymal markersMIR200AMIR200BSFRP1NRG3IL1AKT1ALPLTERTHedgehog signalsMIR429ITGB1DNAZEB2ITGA6CCND1CDH1ERBB4CLDN4Hypoxia signalsTNFMYCTGFB1InvolutionPubertyEmbryonic developmentMAMMARY GLAND DEVELOPMENTPATHWAYPregnancy and lactation


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 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 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 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 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 2.

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Ontology Terms



  1. Katoh M; ''Integrative genomic analyses of ZEB2: Transcriptional regulation of ZEB2 based on SMADs, ETS1, HIF1alpha, POU/OCT, and NF-kappaB.''; Int J Oncol, 2009 PubMed Europe PMC
  2. Smalley M, Ashworth A; ''Stem cells and breast cancer: A field in transit.''; Nat Rev Cancer, 2003 PubMed Europe PMC
  3. Panchal H, Wansbury O, Parry S, Ashworth A, Howard B; ''Neuregulin3 alters cell fate in the epidermis and mammary gland.''; BMC Dev Biol, 2007 PubMed Europe PMC


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102405view18:36, 22 December 2018EgonwReplaced a secondary ChEBI ID with primary ID.
102393view13:22, 22 December 2018DeSlOntology Term : 'milk secreting cell' added !
102392view13:17, 22 December 2018DeSlConnected unconnected lines, added DNA node, changed vertical lines to graohical lines.
102391view13:11, 22 December 2018DeSlAnnotated nodes
88701view16:18, 12 August 2016JmeliusOntology Term : 'regulatory pathway' added !
77104view22:11, 17 July 2014KhanspersOntology Term : 'germ line stem cell' added !
75409view20:36, 28 May 2014Biodados
75408view19:14, 28 May 2014BiodadosModified description
75407view18:43, 28 May 2014BiodadosNew pathway

External references


View all...
NameTypeDatabase referenceComment
AKT1GeneProductENSG00000142208 (Ensembl)
ALPLGeneProductENSG00000162551 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CDH1GeneProductENSG00000039068 (Ensembl)
CLDN4GeneProductENSG00000189143 (Ensembl)
DNAMetaboliteCHEBI:16991 (ChEBI)
ERBB4GeneProductENSG00000178568 (Ensembl)
Hedgehog signalsGeneProduct
Hypoxia signalsGeneProduct
IL1GeneProductIPR000975 (InterPro)
ITGA6GeneProductENSG00000091409 (Ensembl)
ITGB1GeneProductENSG00000150093 (Ensembl)
MIR200AGeneProductENSG00000207607 (Ensembl)
MIR200BGeneProductENSG00000207730 (Ensembl)
MIR429GeneProductENSG00000198976 (Ensembl)
MYCGeneProductENSG00000136997 (Ensembl)
Mesenchymal markersGeneProduct
NRG3GeneProductENSG00000185737 (Ensembl)
SFRP1GeneProductENSG00000104332 (Ensembl)
TERTGeneProductENSG00000164362 (Ensembl)
TGFB1GeneProductENSG00000105329 (Ensembl)
TNFGeneProductENSG00000232810 (Ensembl)
ZEB2GeneProductENSG00000169554 (Ensembl)

Annotated Interactions

No annotated interactions

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