Heart Development (Homo sapiens)

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This pathway has been largely adapted from an article by Deepak Srivastava, Cell. 2006 Sep 22;126(6):1037-48. In this pathway are known transcription factors, miRNAs and regulatory proteins that impact the regional specificity of the human heart. Activating signals are indicated by arrows while inhibitory signals are indicated by T-bars. Special thanks to Kim Cordes for her assistance in revising this pathway, based on recent heart development research.

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  1. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D; ''Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors.''; Cell, 2010 PubMed Europe PMC Scholia
  2. Kwon C, Qian L, Cheng P, Nigam V, Arnold J, Srivastava D; ''A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate.''; Nat Cell Biol, 2009 PubMed Europe PMC Scholia
  3. Srivastava D; ''Making or breaking the heart: from lineage determination to morphogenesis.''; Cell, 2006 PubMed Europe PMC Scholia
  4. Danesh SM, Villasenor A, Chong D, Soukup C, Cleaver O; ''BMP and BMP receptor expression during murine organogenesis.''; Gene Expr Patterns, 2009 PubMed Europe PMC Scholia
  5. Prall OW, Menon MK, Solloway MJ, Watanabe Y, Zaffran S, Bajolle F, Biben C, McBride JJ, Robertson BR, Chaulet H, Stennard FA, Wise N, Schaft D, Wolstein O, Furtado MB, Shiratori H, Chien KR, Hamada H, Black BL, Saga Y, Robertson EJ, Buckingham ME, Harvey RP; ''An Nkx2-5/Bmp2/Smad1 negative feedback loop controls heart progenitor specification and proliferation.''; Cell, 2007 PubMed Europe PMC Scholia
  6. Fulcoli FG, Huynh T, Scambler PJ, Baldini A; ''Tbx1 regulates the BMP-Smad1 pathway in a transcription independent manner.''; PLoS One, 2009 PubMed Europe PMC Scholia
  7. Rivera-Feliciano J, Lee KH, Kong SW, Rajagopal S, Ma Q, Springer Z, Izumo S, Tabin CJ, Pu WT; ''Development of heart valves requires Gata4 expression in endothelial-derived cells.''; Development, 2006 PubMed Europe PMC Scholia
  8. Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D; ''miR-145 and miR-143 regulate smooth muscle cell fate and plasticity.''; Nature, 2009 PubMed Europe PMC Scholia


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106589view19:31, 10 September 2019KhanspersModified description
105613view04:55, 10 August 2019KhanspersModified description
103004view15:04, 31 January 2019Marvin M2Corrected miRNA Ensembl ID
94736view15:02, 5 October 2017Mkutmonfix unconnected line
94735view15:01, 5 October 2017Mkutmonchanged line to graphical line
90186view19:18, 21 October 2016Khanspersfixed unconnected
88633view14:45, 12 August 2016JmeliusOntology Term : 'regulatory pathway' added !
84699view21:21, 15 March 2016KhanspersQuick edit to datanode annotation or property
78590view14:51, 7 January 2015MaintBotadded missing graphIds
73381view05:12, 25 January 2014MaintBotUpdated graphical lines and label backgrounds for new js viewer
69038view17:51, 8 July 2013MaintBotUpdated to 2013 gpml schema
59218view20:13, 22 February 2013MaintBotUpdated Ensembl and UniProt data source
42432view19:12, 24 March 2011NsalomonisSpecify description
42431view19:10, 24 March 2011Nsalomonislegend-layout
42430view19:04, 24 March 2011Samuel SklarSpecify description
42429view19:00, 24 March 2011Samuel SklarSpecify description
42428view18:58, 24 March 2011Samuel SklarSpecify description
42427view18:47, 24 March 2011Samuel SklarPeriodical save, work in progress
42426view18:41, 24 March 2011Samuel SklarSpecify description
42408view19:11, 22 March 2011Samuel SklarSpecify description
42407view18:54, 22 March 2011Samuel SklarSpecify description
42337view20:14, 17 March 2011Samuel SklarOntology Term : 'heart disease' added !
42336view18:15, 17 March 2011MaintBotOntology Term : 'smooth muscle cell neural crest derived' added !
42335view18:12, 17 March 2011MaintBotOntology Term : 'vascular associated smooth muscle cell' added !
42334view18:02, 17 March 2011MaintBotSpecify description
42333view17:59, 17 March 2011MaintBotSpecify description
42332view17:58, 17 March 2011MaintBotSpecify description
42331view17:55, 17 March 2011MaintBotSpecify description
42330view17:48, 17 March 2011MaintBotupdate
41224view23:45, 1 March 2011MaintBotRemoved redundant pathway information and comments
39056view06:21, 1 October 2010NsalomonisSpecify description
39055view06:40, 30 September 2010NsalomonisAdded repogramming factors
39054view06:06, 30 September 2010NsalomonisSpecify description
39053view21:04, 29 September 2010NsalomonisModified description
39052view21:00, 29 September 2010NsalomonisSpecify description
39051view20:57, 29 September 2010NsalomonisModified description
39050view20:53, 29 September 2010NsalomonisModified description
39049view20:47, 29 September 2010NsalomonisSpecify description
39048view20:45, 29 September 2010NsalomonisSpecify description
39045view05:06, 29 September 2010NsalomonisSpecify description
39044view04:57, 29 September 2010NsalomonisSpecify description
39043view04:54, 29 September 2010Nsalomonismoved objects
39042view04:50, 29 September 2010Nsalomonismoved objects
39041view04:46, 29 September 2010Nsalomonismove objects
39040view04:29, 29 September 2010Nsalomonismoved object
39039view04:22, 29 September 2010Nsalomonismoved objects
38458view18:54, 14 September 2010NsalomonisSpecify description
38457view18:49, 14 September 2010NsalomonisK. Cordes edits3
38454view18:11, 14 September 2010NsalomonisK. Cordes edits2
38453view17:59, 14 September 2010NsalomonisPeriodical save, work in progress

External references


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NameTypeDatabase referenceComment
BHLHE40GeneProduct8553 (Entrez Gene) In other species, this is BHLHB2
BMP10GeneProduct27302 (Entrez Gene)
BMP2GeneProduct650 (Entrez Gene)
BMP4GeneProduct652 (Entrez Gene)
BMPR1AGeneProduct657 (Entrez Gene)
BMPR2GeneProduct659 (Entrez Gene)
CTNNB1GeneProduct1499 (Entrez Gene)
ERBB3GeneProduct2065 (Entrez Gene)
FGF10GeneProduct2255 (Entrez Gene)
FGF8GeneProduct2253 (Entrez Gene)
FOXA2GeneProduct3170 (Entrez Gene)
FOXC1GeneProduct2296 (Entrez Gene)
FOXC2GeneProduct2303 (Entrez Gene)
FOXH1GeneProduct8928 (Entrez Gene)
GATA4GeneProduct2626 (Entrez Gene)
GATA6GeneProduct2627 (Entrez Gene)
HAND1GeneProduct9421 (Entrez Gene)
HAND2GeneProduct9464 (Entrez Gene)
HEY1GeneProduct23462 (Entrez Gene)
HEY2GeneProduct23493 (Entrez Gene)
IRX4GeneProduct50805 (Entrez Gene)
ISL1GeneProduct3670 (Entrez Gene)
MAPK1GeneProduct5594 (Entrez Gene)
MEF2CGeneProduct4208 (Entrez Gene)
MIR1-1GeneProductENSG00000199017 (Ensembl Human)
MIR143GeneProductENSG00000208035 (Ensembl Human)
MIR145GeneProductENSG00000207700 (Ensembl Human)
NFATC1GeneProduct4772 (Entrez Gene)
NFATC2GeneProduct4773 (Entrez Gene)
NFATC3GeneProduct4775 (Entrez Gene)
NFATC4GeneProduct4776 (Entrez Gene)
NKX2-5GeneProduct1482 (Entrez Gene)
NOTCH1GeneProduct4851 (Entrez Gene)
PITX2GeneProduct5308 (Entrez Gene)
PTPN11GeneProduct5781 (Entrez Gene)
SHHGeneProduct6469 (Entrez Gene)
SMAD1GeneProduct4086 (Entrez Gene)
SMAD4GeneProduct4089 (Entrez Gene)
SMYD1GeneProduct150572 (Entrez Gene)
SRFGeneProduct6722 (Entrez Gene)
TBX1GeneProduct6899 (Entrez Gene)
TBX20GeneProduct57057 (Entrez Gene)
TBX2GeneProduct6909 (Entrez Gene)
TBX5GeneProduct6910 (Entrez Gene)
VEGFAGeneProduct7422 (Entrez Gene)
VEGFBGeneProduct7423 (Entrez Gene)
VEGFCGeneProduct7424 (Entrez Gene)

Annotated Interactions

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