FGFR3 signalling in chondrocyte proliferation and terminal differentiation (Homo sapiens)

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1Perichondrium/periosteumChondrocyte differentiationproduced by prehypertrophicand hypertrophic chondrocytes Reserve chondrocytesHypertrophic chondrocytesAutophagyEndochondral ossificationPre-hypertrophic chondrocytesWntFGF18PTHLHMAPK12PTH1RATG5MAPK11BMP2SNAI1THRASTAT1MAPK14IHH3,3',5'-TriiodothyronineCNPFGFR3NPR2MAPK13RAF1FGF9PTH1RProliferating chondrocytesBMP4OMIM:215045Chondrodysplasia,Blomstrand typeOMIM:600002Eiken syndromeOMIM:156400Metaphyseal chondrodysplasia,Murk Jansen typeOMIM:187600Thanatophoric dysplasia, type IOMIM:187601Thanatophoric dysplasia, type IIOMIM:616482SADDANOMIM:100800AchondroplasiaOMIM:146000HypochondroplasiaOMIM:610474CATSHL syndromeOMIM:613382Brachydactyly, type E2OMIM:612961Multiple synostoses syndrome 3OMIM:607778Acrocapitofemoral dysplasiaOMIM:112600Brachydactyly, type A2OMIM:602875Acromesomelic dysplasia, Maroteaux typeSOX9RBL1CDKN1ARBL1PPPPPPP2CAChondrocyte proliferationOMIM:612247Crouzon syndrome withacanthosis nigricansOMIM:602849Muenke syndromeOMIM:149730LADD syndromeOMIM:215045Chondrodysplasia,Blomstrand typeOMIM:600002Eiken syndromeOMIM:156400Metaphyseal chondrodysplasia,Murk Jansen typeOMIM:615923Epiphyseal chondrodysplasia, Miura typeOMIM:112500Brachydactyly, type A1Syndactyly Lueken typeMAP2K1MAP2K2MAPK1MAPK3


Description

Taken from Achondroplasia: Development, Pathenogenesis, and Therapy by Ornitz DM, Legeai-Mallet L [1].

Signaling pathways in the postnatal growth plate. During endochondral bone development, FGF9 and FGF18, derived from the perichondrium and surrounding tissue, signal to FGFR3 in chondrocytes. The balance of chondrocyte proliferation and differentiation is controlled by crosstalk of several signaling pathways. Expression of FGFR3 is enhanced by thyroid hormone (T3/3,3',5'-Triiodothyronine) and suppressed by PTHLH (member of the parathyroid hormone family). FGFR3 signaling results in increased expression of Snail1 (encoded by SNAI1), which is required for activation of STAT1 and MAPK signaling (ERK1/2 and p38 branches). Signaling from PTHLH, IHH and BMPs antagonizes the suppression of chondrocyte proliferation by FGFR3. Both FGFR3 and PTHLH function to suppress chondrocyte differentiation and antagonize the action of Wnt signaling, which promotes differentiation. FGFR3 negatively regulates the autophagy protein, ATG5. Activation of downstream signals: PP2a (encoded by PPP2CA) regulates p107 (encoded by RBL1) activation, and STAT1 regulates p21Waf1/Cip1 (encoded by CKDN1A) activation. Both function to suppress chondrocyte proliferation. Activation of the MAPKs, ERK1, and ERK2, regulate Sox9 expression, which functions to suppress chondrocyte terminal differentiation and endochondral ossification.

Linked with a dotted arrow to the GeneProduct nodes are diseases caused by mutation in the respective gene.

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Bibliography

  1. Ornitz DM, Legeai-Mallet L; ''Achondroplasia: Development, pathogenesis, and therapy.''; Dev Dyn, 2017 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
110277view07:08, 2 May 2020EgonwNot a mim-conversion
110263view15:32, 30 April 2020EgonwNot a mim-conversion
110236view15:12, 29 April 2020EgonwNot a mim-conversion
109131view06:31, 18 February 2020RleeFixed unconnected line.
108991view00:07, 13 February 2020Khanspersdecreased BoardHeight
108990view00:07, 13 February 2020Khanspersdecreased BoardHeight
108989view00:06, 13 February 2020Khanspersdecreased BoardHeight and BoardWidth
108988view00:05, 13 February 2020Khanspersdecreased BoardHeight
108768view01:56, 29 January 2020RleeRemoved extra DataNode
108767view01:54, 29 January 2020RleeModified description
108766view01:53, 29 January 2020RleeAdded ERK1/2 branch of MAPK pathway
108739view10:56, 27 January 2020DeSlModified description
108738view10:56, 27 January 2020DeSlOntology Term : 'parathyroid hormone signaling pathway' added !
108737view10:55, 27 January 2020DeSlOntology Term : 'thyroid hormone signaling pathway' added !
108736view10:54, 27 January 2020DeSlOntology Term : 'fibroblast growth factor signaling pathway' added !
108735view10:53, 27 January 2020DeSlOntology Term : 'Muenke Syndrome' added !
108734view10:48, 27 January 2020DeSlModified description
108733view10:36, 27 January 2020DeSlModified description
108732view10:33, 27 January 2020DeSlConverted arrows to graphical lines for disease connectivity.
108643view23:09, 14 January 2020RleeFixed unconnected line.
108622view23:44, 12 January 2020RleeModified description
108621view23:40, 12 January 2020RleeModified title
108620view23:40, 12 January 2020RleeNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
3,3',5'-TriiodothyronineMetaboliteCHEBI:11684 (ChEBI)
ATG5GeneProductENSG00000057663 (Ensembl)
BMP2GeneProductENSG00000125845 (Ensembl)
BMP4GeneProductENSG00000125378 (Ensembl)
CDKN1AGeneProductENSG00000124762 (Ensembl)
CNPGeneProductENSG00000173786 (Ensembl)
FGF18GeneProductENSG00000156427 (Ensembl)
FGF9GeneProductENSG00000102678 (Ensembl)
FGFR3GeneProductENSG00000068078 (Ensembl)
IHHGeneProductENSG00000163501 (Ensembl)
MAP2K1GeneProductENSG00000169032 (Ensembl)
MAP2K2GeneProductENSG00000126934 (Ensembl)
MAPK11GeneProductENSG00000185386 (Ensembl)
MAPK12GeneProductENSG00000188130 (Ensembl)
MAPK13GeneProductENSG00000156711 (Ensembl)
MAPK14GeneProductENSG00000112062 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
NPR2GeneProductENSG00000159899 (Ensembl)
PPP2CAGeneProductENSG00000113575 (Ensembl)
PTH1RGeneProductENSG00000160801 (Ensembl)
PTHLHGeneProductENSG00000087494 (Ensembl)
RAF1GeneProductENSG00000132155 (Ensembl)
RBL1GeneProductENSG00000080839 (Ensembl)
SNAI1GeneProductENSG00000124216 (Ensembl)
SOX9GeneProductENSG00000125398 (Ensembl)
STAT1GeneProductENSG00000115415 (Ensembl)
THRAGeneProductENSG00000126351 (Ensembl)

Annotated Interactions

No annotated interactions

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