BMP signaling in eyelid development (WP3927)

Homo sapiens

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 [https://assays.cancer.gov/available_assays?wp_id=WP3927 CPTAC Assay Portal]

Authors

Kristina Hanspers , Egon Willighagen , and Eric Weitz

Activity

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Cited In

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Organisms

Homo sapiens

Communities

Annotations

Pathway Ontology

signaling pathway pertinent to development

Participants

Label Type Compact URI Comment
FGF10 GeneProduct ensembl:ENSG00000070193 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000021732
FGFR2 GeneProduct ensembl:ENSG00000066468 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000030849
INHBB GeneProduct ensembl:ENSG00000163083 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000037035
TGFA GeneProduct ensembl:ENSG00000163235 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000029999
SHH GeneProduct ensembl:ENSG00000164690 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000002633
BMP4 GeneProduct ensembl:ENSG00000125378 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000021835
SFRP1 GeneProduct ensembl:ENSG00000104332 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000031548
SMAD1 GeneProduct ensembl:ENSG00000170365 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000031681
SMAD5 GeneProduct ensembl:ENSG00000113658 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000021540
SMAD4 GeneProduct ensembl:ENSG00000141646 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000024515
PITX2 GeneProduct ensembl:ENSG00000164093 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000028023
DKK2 GeneProduct ensembl:ENSG00000155011 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000028031
FOXC1 GeneProduct ensembl:ENSG00000054598 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000050295
FOXC2 GeneProduct ensembl:ENSG00000176692 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000046714
NOTCH1 GeneProduct ensembl:ENSG00000148400 Notch Not Specified
Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000026923
MAP3K1 GeneProduct ensembl:ENSG00000095015 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000021754
MAPK9 GeneProduct ensembl:ENSG00000050748 JNK Not Specified
Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000020366
JUN GeneProduct ensembl:ENSG00000177606 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000052684
EGFR GeneProduct ensembl:ENSG00000146648 Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000020122
MAPK3 GeneProduct ensembl:ENSG00000102882 ERK Not Specified
Homology Mapping from Mus musculus to Homo sapiens: Original ID = En:ENSMUSG00000063065

References

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