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Involvement of a novel Tnf receptor homologue in hair follicle induction

Nature Genetics volume 22, pages 370–374 (1999)Cite this article

Abstract

Although inductive interactions are known to be essential for specification of cell fate in many vertebrate tissues, the signals and receptors responsible for transmitting this information remain largely unidentified. Mice with mutations in the downless (dl) gene have defects in hair follicle induction, lack sweat glands and have malformed teeth1. These structures originate as ectodermal placodes, which invaginate into the underlying mesenchyme and differentiate to form specific organs2,3,4. Positional cloning of the dl gene began with identification of the transgenic family OVE1. One branch of the family, dlOVE1B, carries an approximately 600-kb deletion at the dl locus caused by transgene integration. The mutated locus has been physically mapped in this family5, and a 200-kb mouse YAC clone, YAC D9, has been identified and shown to rescue the dl phenotype in the spontaneous dlJackson (dlJ, recessive) and Dlsleek (Dlslk, dominant negative) mutants6. Here we report the positional cloning of the dl gene, which encodes a novel member of the tumour necrosis factor (Tnf) receptor (Tnfr) family. The mutant phenotype and dl expression pattern suggests that this gene encodes a receptor that specifies hair follicle fate. Its ligand is likely to be the product of the tabby (Ta) gene, as Ta mutants have a phenotype identical to that of dl (ref. 1) mutants and Ta encodes a Tnf-like protein.

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Figure 1: Domain structure and amino acid alignments of Edar.
Figure 2: Analysis of dl transcripts.
Figure 3: Expression of dl in skin.
Figure 4: Absence of expression of early hair follicle markers in dl mutant skin.
Figure 5: Whole-mount in situ hybridization of dl to an E15 OVE 951 embryo.

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Acknowledgements

We thank K. Majumder for sharing unpublished data and reagents; D. Roop and A. Schumacher for critically reading this manuscript; A. McMahon for providing Shh cDNA; and the Genetics Institute, Inc., for providing Bmp4 cDNA. This research was supported by NIH grants AR45316 and HL49953.

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  1. Department of Cell Biology, Baylor College of Medicine, Houston, 77030, Texas, USA

    Denis J. Headon & Paul A. Overbeek

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  1. Denis J. Headon
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Correspondence to Paul A. Overbeek.

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Headon, D., Overbeek, P. Involvement of a novel Tnf receptor homologue in hair follicle induction . Nat Genet 22, 370–374 (1999). https://doi.org/10.1038/11943

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