Localization of Shh expression by Wnt and Eda affects axial polarity and shape of hairs.
Axial patterning is a recurrent theme during embryonic development. To elucidate its fundamental principles, the hair follicle is an attractive model due to its easy accessibility and dispensability. Hair follicle asymmetry is evident from its angling and the localization of associated structures. However, axial patterning is not restricted to the follicle itself but also generates rotational hair shaft asymmetry which, for zigzag hairs, generates 3-4 bends that alternately point into opposite directions. Here we show by analyzing mutant and transgenic mice that WNT and ectodysplasin signaling are involved in the control of the molecular and morphological asymmetry of the follicle and the associated hair shaft, respectively. Asymmetry is affected by polarized WNT and ectodysplasin signaling in mature hair follicles. When endogenous signaling is impaired, molecular asymmetry is lost and mice no longer form zigzag hairs. Both signaling pathways affect the polarized expression of Shh which likely functions as a directional reference for hair shaft production in all follicles. We propose that this regulatory pathway also establishes follicular asymmetry during morphogenesis. Moreover, the identified molecular hierarchy offers a model for the periodic patterning of zigzag hairs mechanistically similar to mesodermal segmentation.
Hammerschmidt
Brigitte
B
Max-Planck Institute of Immunobiology, Stuebeweg 51, 79108 Freiburg, Germany.
Schlake
Thomas
T
D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D017931:DNA Primers; D053331:Ectodysplasins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D018859:Hair Follicle / Q000196:embryology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
D017931:DNA Primers; C501127:Dkk1 protein, mouse; D053331:Ectodysplasins; C506019:Eda protein, mouse; D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; C465570:Shh protein, mouse; D051153:Wnt Proteins; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D001616:beta-Galactosidase