Foxn1 is required for tissue assembly and desmosomal cadherin expression in the hair shaft

The mouse nude mutation inactivates the gene encoding the Foxn1 transcription factor, causing defective hair morphogenesis. Here, we show for the first time that Foxn1 is required for proper assembly of the hair medulla, and we identify Foxn1‐regulated genes by transcript profiling. One such gene encodes the desmosomal cadherin, Dsc2. Significantly, Foxn1‐dependent Dsc2 expression is restricted to the hair medulla, and within these cells, Dsc2 protein is predominantly localized to specialized adhesion junctions between the cortex and the medulla. Our results reveal Foxn1 as an essential regulator of tissue assembly in the growing hair shaft and implicate Dsc2 as a downstream effector of this activity. Developmental Dynamics 232:1062–1068, 2005. © 2005 Wiley‐Liss, Inc.

[1]  B. Kyewski,et al.  Two Genetically Separable Steps in the Differentiation of Thymic Epithelium , 1996, Science.

[2]  D. Garrod,et al.  Desmosomes: differentiation, development, dynamics and disease. , 1996, Current opinion in cell biology.

[3]  A. Magee,et al.  Molecular map of the desmosomal plaque. , 1999, Journal of cell science.

[4]  M. Ko,et al.  Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[5]  T. Schlake,et al.  Forkhead/winged‐helix transcription factor whn regulates hair keratin gene expression: Molecular analysis of the Nude skin phenotype , 2000, Developmental dynamics : an official publication of the American Association of Anatomists.

[6]  Thomas Boehm,et al.  New member of the winged-helix protein family disrupted in mouse and rat nude mutations , 1994, Nature.

[7]  Elaine Fuchs,et al.  Intercellular adhesion, signalling and the cytoskeleton , 2002, Nature Cell Biology.

[8]  J. Brissette,et al.  Association between mouse nude gene expression and the initiation of epithelial terminal differentiation. , 1999, Developmental biology.

[9]  T. Boehm,et al.  Laser capture microdissection‐based expression profiling identifies PD1‐ligand as a target of the nude locus gene product , 2001, European journal of immunology.

[10]  J. Sundberg,et al.  The nude mouse skin phenotype: the role of Foxn1 in hair follicle development and cycling. , 2001, Experimental and molecular pathology.

[11]  R. Paus,et al.  Mutant laboratory mice with abnormalities in hair follicle morphogenesis, cycling, and/or structure: annotated tables , 2001, Experimental dermatology.

[12]  H. Merker,et al.  Nude Mice Are Not Hairless , 1990 .

[13]  J. Sundberg Handbook of Mouse Mutations with Skin and Hair Abnormalities , 1994 .

[14]  J. Brissette,et al.  Ectopic expression of the nude gene induces hyperproliferation and defects in differentiation: implications for the self-renewal of cutaneous epithelia. , 1999, Developmental biology.

[15]  T. Boehm,et al.  The whn transcription factor encoded by the nude locus contains an evolutionarily conserved and functionally indispensable activation domain. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  S. Tsuchimoto,et al.  Gene expression of mouse S100A3, a cysteine-rich calcium-binding protein, in developing hair follicle. , 1998, The Journal of investigative dermatology.

[17]  J. Smith,et al.  Bix1, a direct target of Xenopus T-box genes, causes formation of ventral mesoderm and endoderm. , 1998, Development.

[18]  T. Schlake,et al.  Expression domains in the skin of genes affected by the nude mutation and identified by gene expression profiling , 2001, Mechanisms of Development.

[19]  A. Furley,et al.  Complete rescue of the nude mutant phenotype by a wild-type Foxn1 transgene , 2002, Mammalian Genome.

[20]  T. Schlake,et al.  Genetically separable determinants of hair keratin gene expression , 2000, Developmental dynamics : an official publication of the American Association of Anatomists.

[21]  E. Fuchs,et al.  At the roots of a never-ending cycle. , 2001, Developmental cell.

[22]  T. Sun,et al.  Acidic and basic hair/nail ("hard") keratins: their colocalization in upper cortical and cuticle cells of the human hair follicle and their relationship to "soft" keratins , 1986, The Journal of cell biology.

[23]  R. Paus,et al.  What controls hair follicle cycling? , 1999, Experimental dermatology.

[24]  T. Sun,et al.  Interaction of trichohyalin with intermediate filaments: three immunologically defined stages of trichohyalin maturation. , 1992, The Journal of investigative dermatology.

[25]  Kathleen J. Green,et al.  Are desmosomes more than tethers for intermediate filaments? , 2000, Nature Reviews Molecular Cell Biology.