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First published online 1 June 2005
doi: 10.1242/dev.01873

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FGF signals specifically regulate the structure of hair shaft medulla via IGF-binding protein 5

Max-Planck-Institute of Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany

View larger version (95K): [in a new window]   Fig. 1. Foxn1::dnFgfr2-IIIb transgenic mice develop abnormal hair coats. (A-D) All transgenic mouse lines show strong expression of dnFgfr2-IIIb, as demonstrated by non-radioactive in situ hybridisation. Nevertheless, transcript levels are significantly different, especially between line #53 and lines #42 and #8. The inset in B shows transgene expression in line #53 after extended staining whereas the inset in (A) shows endogenous gene expression of a corresponding wild-type section. The inset in D demonstrates the expression pattern of the endogenous Foxn1 gene, which is identical to that of the dnFgfr2-IIIb transgene under the control of a 30 kb Foxn1 promoter fragment (B-D). (E-H) Strong transgene expression causes a silky hair coat appearance. During early development of the pelage, it also appears to be less dense in transgenic mice when compared with their wild-type littermates; body skin is still visible at day 10 after birth (F). Scale bars: 100 µm.

View larger version (103K): [in a new window]   Fig. 2. The number of medulla columns is reduced in Foxn1::dnFgfr2-IIIb transgenic mice. (A-C) A comparison of hair coat composition demonstrates that transgenic mice still possess all four hair types present in wild-type animals. The overall length and shape of hairs is shown at the top, whereas the microscopic appearance of the hair shaft structure is shown at the bottom. The length of hair shafts is not affected. In wild-type mice, the number of medulla columns differs between single hairs of the awl and auchene type (A). In the strong expressing lines #8 and #42 the number of medulla columns is generally reduced to one (B). The number is reduced by one in guard, awl and auchene hairs of line #53, preserving the heterogeneity of hair shaft structures of awl and auchene hairs (C). a, awl hair; au, auchene hair; g, guard hair; z, zigzag hair. (D,E) Histological analyses of hair follicles reveal an abnormal structure of the medulla. (F,G) The matrix and medulla of wild-type and transgenic hair follicles do not contain TUNEL-positive cells. (H,I) The proliferative compartment of hair follicles is largely unaffected by transgene expression as demonstrated by Ki67 staining. In some wild-type follicles, the zone of proliferating cells next to the dermal papilla appears to extend more along the proximodistal axis than in more lateral parts of the proliferative compartment (arrowheads). Such an extension has never been observed in transgenic follicles. Scale bars: 50 µm.

View larger version (91K): [in a new window]   Fig. 3. Specific molecular defects in Foxn1::dnFgfr2-IIIb transgenic mice. Expression of markers of the hair shaft medulla was analysed by non-radioactive in situ hybridisation in wild-type (A,C,E,G,I,K) and transgenic (B,D,F,H,J,L) hair follicles during the growth phase. Transcription of involucrin (C,D), K6hf (E,F), Sh3d19 (G,H) and Pai2 (I,J) is severely reduced in transgenic hair follicles, while expression of arachidonate 8(S) lipoxygenase (A,B) and Foxq1 (K,L) is normal. Scale bars: 100 µm.

View larger version (109K): [in a new window]   Fig. 4. Molecular abnormalities in Foxn1::dnFgfr2-IIIb transgenic mice are restricted to the medulla. Differential gene expression in wild-type (A,C,E,G,I) and transgenic (B,D,F,H,J) hair follicles that has been identified by microarray analyses was confirmed by non-radioactive in situ hybridisation. Gene expression is either strongly downregulated (A-D) or significantly upregulated (E-J) in the medulla of transgenic follicles. Whereas Igfbp5 is markedly expressed in small follicles of wild-type skin (G), large guard hair follicles show only weak signals (I). Scale bars: 100 µm.

View larger version (61K): [in a new window]   Fig. 5. Expression of Igfbp5 in the hair follicle reduces the number of medulla columns. Transgenic expression of Igfbp5 in hair follicles during the growth phase using the involucrin promoter decreases the length of hair shafts (top) and reduces the number of air space columns to one (bottom). The extraordinary thinness of hair shafts severely hampered the isolation of intact hairs. Thus, the presence of auchene hairs could not unequivocally be confirmed.

View larger version (18K): [in a new window]   Fig. 6. Model for the effect of FGF signals on the follicular expression of Igfbp5 and on the structure of the hair shaft medulla. Whereas the expression of Fgfr2 in the hair matrix has been previously demonstrated, the assumption of Fgfr2-IIIb expression in the precursors of the hair medulla is based on the presented data.

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