Mammary gland development: embryonic development - stage 1 of 4 (Homo sapiens)

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133332332233323333333Cell junctionTERTITGA6MIR429Hedgehog signalsCDH1PubertyMIR200ACCND1NRG3IL1CLDN4DNAZEB2MYCHypoxia signalsTGFB1Mesenchymal markersSFRP1MIR200BERBB4ALPLITGB1AKT1TNFMammary gland development pathwayInvolutionPregnancy and lactationEmbryonic development


Description

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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Bibliography

  1. Smalley M, Ashworth A; ''Stem cells and breast cancer: A field in transit.''; Nat Rev Cancer, 2003 PubMed Europe PMC Scholia
  2. 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 Scholia
  3. 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 Scholia

History

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CompareRevisionActionTimeUserComment
129077view14:37, 10 March 2024EweitzModified title
128673view13:31, 19 February 2024EweitzUntangle interactions, economize layout
128672view13:27, 19 February 2024EweitzUpdate top nodes
128666view12:44, 19 February 2024EweitzFix site-invisible lines, refine top graphics, identify pathways
128663view02:26, 19 February 2024EweitzFix truncated node, economize layout
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

DataNodes

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NameTypeDatabase referenceComment
AKT1GeneProductENSG00000142208 (Ensembl)
ALPLGeneProductENSG00000162551 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CDH1GeneProductENSG00000039068 (Ensembl)
CLDN4GeneProductENSG00000189143 (Ensembl)
DNAMetaboliteCHEBI:16991 (ChEBI)
ERBB4GeneProductENSG00000178568 (Ensembl)
Embryonic developmentPathwayWP2813 (WikiPathways)
Hedgehog signalsGeneProduct
Hypoxia signalsGeneProduct
IL1GeneProductIPR000975 (InterPro)
ITGA6GeneProductENSG00000091409 (Ensembl)
ITGB1GeneProductENSG00000150093 (Ensembl)
InvolutionPathwayWP2815 (WikiPathways)
MIR200AGeneProductENSG00000207607 (Ensembl)
MIR200BGeneProductENSG00000207730 (Ensembl)
MIR429GeneProductENSG00000198976 (Ensembl)
MYCGeneProductENSG00000136997 (Ensembl)
Mesenchymal markersGeneProduct
NRG3GeneProductENSG00000185737 (Ensembl)
Pregnancy and lactationPathwayWP2817 (WikiPathways)
PubertyPathwayWP2814 (WikiPathways)
SFRP1GeneProductENSG00000104332 (Ensembl)
TERTGeneProductENSG00000164362 (Ensembl)
TGFB1GeneProductENSG00000105329 (Ensembl)
TNFGeneProductENSG00000232810 (Ensembl)
ZEB2GeneProductENSG00000169554 (Ensembl)

Annotated Interactions

No annotated interactions

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