Dr. Perälä's present address is Cell and Molecular Biology Program, Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Expression of Foxi3 is regulated by ectodysplasin in skin appendage placodes
Version of Record online: 9 APR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 242, Issue 6, pages 593–603, June 2013
How to Cite
Shirokova, V., Jussila, M., Hytönen, M. K., Perälä, N., Drögemüller, C., Leeb, T., Lohi, H., Sainio, K., Thesleff, I. and Mikkola, M. L. (2013), Expression of Foxi3 is regulated by ectodysplasin in skin appendage placodes. Dev. Dyn., 242: 593–603. doi: 10.1002/dvdy.23952
Drs. Shirokova, Jussila, and Hytönen contributed equally to this work.
- Issue online: 20 MAY 2013
- Version of Record online: 9 APR 2013
- Accepted manuscript online: 26 FEB 2013 12:00AM EST
- Manuscript Accepted: 14 FEB 2013
- Manuscript Revised: 12 FEB 2013
- Manuscript Received: 24 SEP 2012
- Swiss National Science Foundation. Grant Number: CRSI33_125459
- Sigrid Jusélius Foundation
- Academy of Finland
- ectodermal dysplasia;
- tooth development;
- hair follicle development
Background: Foxi3 is a member of the large forkhead box family of transcriptional regulators, which have a wide range of biological activities including manifold developmental processes. Heterozygous mutation in Foxi3 was identified in several hairless dog breeds characterized by sparse fur coat and missing teeth. A related phenotype called hypohidrotic ectodermal dysplasia (HED) is caused by mutations in the ectodysplasin (Eda) pathway genes. Results: Expression of Foxi3 was strictly confined to the epithelium in developing ectodermal appendages in mouse embryos, but no expression was detected in the epidermis. Foxi3 was expressed in teeth and hair follicles throughout embryogenesis, but in mammary glands only during the earliest stages of development. Foxi3 expression was decreased and increased in Eda loss- and gain-of-function embryos, respectively, and was highly induced by Eda protein in embryonic skin explants. Also activin A treatment up-regulated Foxi3 mRNA levels in vitro. Conclusions: Eda and activin A were identified as upstream regulators of Foxi3. Foxi3 is a likely transcriptional target of Eda in ectodermal appendage placodes suggesting that HED phenotype may in part be produced by compromised Foxi3 activity. In addition to hair and teeth, Foxi3 may have a role in nail, eye, and mammary, sweat, and salivary gland development. Developmental Dynamics 242:593–603, 2013. © 2013 Wiley Periodicals, Inc.