A crucial role for Fgfr2-IIIb signalling in epidermal development and hair follicle patterning.
To understand the role Fgf signalling in skin and hair follicle development, we analysed the phenotype of mice deficient for Fgfr2-IIIb and its main ligand Fgf10. These studies showed that the severe epidermal hypoplasia found in mice null for Fgfr2-IIIb is caused by a lack of the basal cell proliferation that normally results in a stratified epidermis. Although at term the epidermis of Fgfr2-IIIb null mice is only two to three cells thick, it expresses the classical markers of epidermal differentiation and establishes a functional barrier. Mice deficient for Fgf10 display a similar but less severe epidermal hypoplasia. By contrast, Fgfr2-IIIb-/-, but not Fgf10-/-, mice produced significantly fewer hair follicles, and their follicles were developmentally retarded. Following transplantation onto nude mice, grafts of Fgfr2-IIIb-/- skin showed impaired hair formation, with a decrease in hair density and the production of abnormal pelage hairs. Expression of Lef1, Shh and Bmp4 in the developing hair follicles of Fgfr2-IIIb-/- mice was similar to wild type. These results suggest that Fgf signalling positively regulates the number of keratinocytes needed to form a normal stratified epidermis and to initiate hair placode formation. In addition, Fgf signals are required for the growth and patterning of pelage hairs.
Petiot
Anita
A
Cancer Research UK, London Research Institute, 61 Lincoln's Inn Fields, London WC2A 3PX, UK.
Conti
Francesco J A
FJ
Grose
Richard
R
Revest
Jean-Michel
JM
Hodivala-Dilke
Kairbaan M
KM
Dickson
Clive
C
D000818:Animals; D004817:Epidermis / Q000196:embryology* / Q000473:pathology; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018859:Hair Follicle / Q000196:embryology* / Q000473:pathology; D051379:Mice; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016038:Skin Transplantation
C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; C496354:Fgfr2 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051497:Receptor, Fibroblast Growth Factor, Type 2