BMP signaling in eyelid development (WP3927)

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. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]
last edited


Khanspers, Egonw, and Eweitz

Cited In


Homo sapiens



Pathway Ontology: signaling pathway pertinent to development signaling pathway pertinent to development


Label Type Compact Identifier
SFRP1 GeneProduct ensembl:ENSG00000104332
SMAD5 GeneProduct ensembl:ENSG00000113658
PITX2 GeneProduct ensembl:ENSG00000164093
Wnt Canonical Signaling Pathway wikipathways:WP428
INHBB GeneProduct ensembl:ENSG00000163083
SMAD4 GeneProduct ensembl:ENSG00000141646
MAP3K1 GeneProduct ensembl:ENSG00000095015
EGFR GeneProduct ensembl:ENSG00000146648
Bmp Canonical Signaling Pathway wikipathways:WP3931
DKK2 GeneProduct ensembl:ENSG00000155011
SHH GeneProduct ensembl:ENSG00000164690
MAPK3 GeneProduct ensembl:ENSG00000102882
NOTCH1 GeneProduct ensembl:ENSG00000148400
FGF10 GeneProduct ensembl:ENSG00000070193
FOXC2 GeneProduct ensembl:ENSG00000176692
FOXC1 GeneProduct ensembl:ENSG00000054598
SMAD1 GeneProduct ensembl:ENSG00000170365
TGFA GeneProduct ensembl:ENSG00000163235
FGFR2 GeneProduct ensembl:ENSG00000066468
BMP4 GeneProduct ensembl:ENSG00000125378
MAPK9 GeneProduct ensembl:ENSG00000050748
JUN GeneProduct ensembl:ENSG00000177606


  1. Huang J, Dattilo LK, Rajagopal R, Liu Y, Kaartinen V, Mishina Y, et al. FGF-regulated BMP signaling is required for eyelid closure and to specify conjunctival epithelial cell fate. Development. 2009 May;136(10):1741–50. PubMed Europe PMC Scholia