Title:Fgf10: A Paracrine-Signaling Molecule in Development, Disease, and Regenerative Medicine
Volume: 14
Issue: 4
Author(s): N. Itoh and H. Ohta
Affiliation:
Keywords:
Development, disease, Fgf, Fgf10, Fgfr2b, paracrine, stem cells.
Abstract: The Fgf family comprises 22 members with diverse functions in development, repair, metabolism,
and neuronal activities. Fgf10 mediates biological responses by activating Fgf receptor 2b (Fgfr2b) with
heparin/heparan sulfate in a paracrine manner. Fgf10 and Fgfr2b are expressed in mesenchymal and epithelial
tissues, respectively. Fgf10 is an epithelial-mesenchymal signaling molecule. Fgf10 knockout mice show
severe phenotypes with complete truncation of the fore- and hindlimbs and die shortly after birth due to
impaired lung development, indicating that Fgf10 serves as an essential regulator of lung and limb formation.
Fgf10 also has roles in the development of white adipose tissue, heart, liver, brain, kidney, cecum, ocular
glands, thymus, inner ear, tongue, trachea, eye, stomach, prostate, salivary gland, mammary gland, and
whiskers. The diverse phenotypes of Fgf10 knockout mice are closely related to those of Fgfr2 knockout mice,
suggesting that Fgf10 acts as a major ligand for Fgfr2b in mouse multi-organ development. Aplasia of lacrimal
and salivary glands and lacrimo-auriculo-dento-digital syndrome are caused by Fgf10 mutations in humans.
Variants in Fgf10 may be involved in an increased risk for limb deficiencies and cleft lip and palate. Patients
with Fgf10 haploinsufficiency have lung function parameters indicating chronic obstructive pulmonary disease.
Fgf10 induces migration and invasion in pancreatic cancer cells. Fgf10 signaling may be involved in an
increased risk for breast cancer. Fgf10 also induces the differentiation of embryonic stem cells into a gut-like
structure, cardiomyocytes, and hepatocytes. These findings indicate the crucial roles of Fgf10 in development,
disease, and regenerative medicine.
