During embryonic development, the epidermis differentiates into a variety of different structures, including hair follicles, sweat glands,, Meibomian glands and teeth. Although the formation of these epidermal derivatives is known to require inductive interactions between the epidermal cells and the adjacent dermal mesenchyme, the signals responsible for initiating these alternative pathways of development have been difficult to identify. In mice, there are three mutations that may be relevant to the inductive process. The mutations are named Tabby (Ta, X chromosome) downless (dl, chromosome 10) and crinkled (cr, chromosome 13). Mutations in these genes produce the same mutant phenotype, suggesting that the genes encode proteins that interact with each other. The mutant mice are missing 3 of the 4 normal types of hair. They have no hair on their tails or behind their ears, no sweat glands, no Meibomian glands, defects in their teeth, and a distinctive kink at the tip of the tail. The mutant phenotype resembles a human condition as anhidrotic (or hypohidrotic) ectodermal based on a transgenic family with an insertional mutation, we have been able to identify the coding sequences for the downless gene. The gene encodes a transmembrane receptor with homology to the TNF receptor family. We have also recently shown that Tabby encodes a ligand for downless and has TNF homology. The one gene that remains to be cloned is crinkled. In order to clone and characterize this gene, our specific aims are: 1) To analyze and evaluate candidates crinkled cDNAs; 2) To analyze how Crinkled transduces the Edar signal; 3) To elucidate the intracellular signal transduction mechanisms downstream from Edar/Cr; and 4) To establish an inducible system for expression of the Cr and EDAR proteins kin the skin of transgenic mice. These studies will help define the molecular basis for an inductive program that specifies cell fate in the epidermis.
| Hoelzl, Maria A; Heby-Henricson, Karin; Gerling, Marco et al. (2017) Differential requirement of SUFU in tissue development discovered in a hypomorphic mouse model. Dev Biol 429:132-146 |
| Rice, Robert H; Durbin-Johnson, Blythe P; Ishitsuka, Yosuke et al. (2016) Proteomic Analysis of Loricrin Knockout Mouse Epidermis. J Proteome Res 15:2560-6 |
| Ishitsuka, Yosuke; Huebner, Aaron J; Rice, Robert H et al. (2016) Lce1 Family Members Are Nrf2-Target Genes that Are Induced to Compensate for the Loss of Loricrin. J Invest Dermatol 136:1656-1663 |
| Zhang, Cong; Large, Michael J; Duggavathi, Raj et al. (2013) Liver receptor homolog-1 is essential for pregnancy. Nat Med 19:1061-6 |
| Fiaschi, Marie; Kolterud, Asa; Nilsson, Mats et al. (2011) Targeted expression of GLI1 in the salivary glands results in an altered differentiation program and hyperplasia. Am J Pathol 179:2569-79 |
| Dai, Daisy; Zhu, Huiping; Wlodarczyk, Bogdan et al. (2011) Fuz controls the morphogenesis and differentiation of hair follicles through the formation of primary cilia. J Invest Dermatol 131:302-10 |
| Honeycutt, Kimberly A; Waikel, Rebekah L; Koster, Maranke I et al. (2010) The effect of c-myc on stem cell fate influences skin tumor phenotype. Mol Carcinog 49:315-9 |
| Jaks, Viljar; Kasper, Maria; Toftgard, Rune (2010) The hair follicle-a stem cell zoo. Exp Cell Res 316:1422-8 |
| Ulvmar, Maria H; Sur, Inderpreet; Mémet, Sylvie et al. (2009) Timed NF-kappaB inhibition in skin reveals dual independent effects on development of HED/EDA and chronic inflammation. J Invest Dermatol 129:2584-93 |
| Kim, Soeun; Choi, Irene F; Quante, Jessica R et al. (2009) p63 directly induces expression of Alox12, a regulator of epidermal barrier formation. Exp Dermatol 18:1016-21 |
Showing the most recent 10 out of 53 publications
