BMP Signaling Pathway in Eyelid Development (Mus musculus)

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1Meibomian GlandConjunctival Cell FateEyelid ClosurePeriderm MigrationEyelid ClosureConjunctiva Proliferation andPrecocious DifferentiationTranslocation intoNucleusTransdifferentiation of MeibomianGland into Hair FollicleMEKK1Dkk2Smad5Fgf10Bmp4Sfrp1ShhBmp Canonical SignalingFoxc1Smad4Foxc2TgfaNotchFgfr2Wnt Canonical Signalingp-c-JunERKActivin beta-BSmad1EgfrJNKPitx2


The signaling pathways involved in eyelid development are displayed with interactions that are known (solid arrows) and proposed (dotted arrows). The four main pathways shown are activated by Fgf10 and regulate key processes, but also interact with each other. The first pathway is a proposed promotion of sfrp1 which inhibits Wnt that regulates the Meibomian Gland. The Wnt pathway also activates pitx2 and begins the proposed pathway to eyelid closure. The second pathway begins with Fgfr2 activating Bmp4, a protein that may also be regulated by Shh, and continuing through a protein chain to regulate conjunctival cell fate. In this pathway Bmp also inhibits transdifferentiation of Meibomian Gland into a hair follicle, conjunctiva proliferation, and precocious differentiation. The last two pathways are linked to the regulation of eyelid closure through a cascade of protein activation and is further promoted by Bmp through stimulation of phosphorylated c-Jun. This pathway is based on figure 10B from Huang et al.

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  1. Huang J, Dattilo LK, Rajagopal R, Liu Y, Kaartinen V, Mishina Y, Deng CX, Umans L, Zwijsen A, Roberts AB, Beebe DC; ''FGF-regulated BMP signaling is required for eyelid closure and to specify conjunctival epithelial cell fate.''; Development, 2009 PubMed Europe PMC Scholia


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111760view17:41, 4 September 2020DeSlChanged ID for Wnt Canonical Signaling to ID (iso name)
90081view05:16, 13 October 2016KhanspersModified title
88551view01:40, 11 August 2016AAR&CoAdded Data Node
88550view01:37, 11 August 2016AAR&CoEdited Labels
88548view01:34, 11 August 2016AAR&CoFixed Interactions
87671view08:55, 25 July 2016LindarieswijkOntology Term : 'signaling pathway pertinent to development' added !
85956view19:49, 21 June 2016AAR&CoAdjust canonical pathways
85946view19:07, 21 June 2016AAR&CoSignaling pathway nodes changed
85933view18:31, 21 June 2016AAR&CoFixed Unconnected Line
85932view18:30, 21 June 2016AAR&CoModified description
85867view23:19, 18 June 2016AAR&CoModified description
85866view21:46, 18 June 2016AAR&CoNew pathway

External references


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NameTypeDatabase referenceComment
Activin beta-BGeneProductENSMUSG00000037035 (Ensembl)
Bmp Canonical SignalingPathwayWP339 (WikiPathways) Identifier Not Found
Bmp4GeneProductENSMUSG00000021835 (Ensembl)
Dkk2GeneProductENSMUSG00000028031 (Ensembl)
ERKGeneProductENSMUSG00000063065 (Ensembl) ERK Not Specified
EgfrGeneProductENSMUSG00000020122 (Ensembl)
Fgf10GeneProductENSMUSG00000021732 (Ensembl)
Fgfr2GeneProductENSMUSG00000030849 (Ensembl)
Foxc1GeneProductENSMUSG00000050295 (Ensembl)
Foxc2GeneProductENSMUSG00000046714 (Ensembl)
JNKGeneProductENSMUSG00000020366 (Ensembl) JNK Not Specified
MEKK1GeneProductENSMUSG00000021754 (Ensembl)
NotchGeneProductENSMUSG00000026923 (Ensembl) Notch Not Specified
Pitx2GeneProductENSMUSG00000028023 (Ensembl)
Sfrp1GeneProductENSMUSG00000031548 (Ensembl)
ShhGeneProductENSMUSG00000002633 (Ensembl)
Smad1GeneProductENSMUSG00000031681 (Ensembl)
Smad4GeneProductENSMUSG00000024515 (Ensembl)
Smad5GeneProductENSMUSG00000021540 (Ensembl)
TgfaGeneProductENSMUSG00000029999 (Ensembl)
Wnt Canonical SignalingPathwayWP403 (WikiPathways)
p-c-JunGeneProductENSMUSG00000052684 (Ensembl)

Annotated Interactions

No annotated interactions

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