Stimulation of ectodermal organ development by Ectodysplasin-A1.
Organs developing as ectodermal appendages share similar early morphogenesis and molecular mechanisms. Ectodysplasin, a signaling molecule belonging to the tumor necrosis factor family, and its receptor Edar are required for normal development of several ectodermal organs in humans and mice. We have overexpressed two splice forms of ectodysplasin, Eda-A1 and Eda-A2, binding to Edar and another TNF receptor, Xedar, respectively, under the keratin 14 (K14) promoter in the ectoderm of transgenic mice. Eda-A2 overexpression did not cause a detectable phenotype. On the contrary, overexpression of Eda-A1 resulted in alterations in a variety of ectodermal organs, most notably in extra organs. Hair development was initiated continuously from E14 until birth, and in addition, the transgenic mice had supernumerary teeth and mammary glands, phenotypes not reported previously in transgenic mice. Also, hair composition and structure was abnormal, and the cycling of hairs was altered so that the growth phase (anagen) was prolonged. Both hairs and nails grew longer than normal. Molar teeth were of abnormal shape, and enamel formation was severely disturbed in incisors. Furthermore, sweat gland function was stimulated and sebaceous glands were enlarged. We conclude that ectodysplasin-Edar signaling has several roles in ectodermal organ development controlling their initiation, as well as morphogenesis and differentiation.
Mustonen
Tuija
T
Developmental Biology Program, Institute of Biotechnology, Viikki Biocenter, University of Helsinki, 00014 Helsinki, Finland.
Pispa
Johanna
J
Mikkola
Marja L
ML
Pummila
Marja
M
Kangas
Aapo T
AT
Pakkasjärvi
Leila
L
Jaatinen
Risto
R
Thesleff
Irma
I
D000818:Animals; D003743:Dental Enamel / Q000196:embryology; D004475:Ectoderm / Q000502:physiology*; D053331:Ectodysplasins; D006197:Hair / Q000196:embryology*; D008321:Mammary Glands, Animal / Q000196:embryology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D014070:Tooth / Q000196:embryology*
D053331:Ectodysplasins; C506019:Eda protein, mouse; D008565:Membrane Proteins