The Nude Mutant Gene Foxn1 Is a HOXC13 Regulatory Target During Hair Follicle and Nail Differentiation

December 2010 in “ The journal of investigative dermatology/Journal of investigative dermatology ”

Christopher S. Potter, Nathanael Pruett, Michael J. Kern, Mary Ann Baybo, Alan R. Godwin, Kathleen A. Potter, Ron L. Peterson, John P. Sundberg, Alexander Awgulewitsch

Hoxc13 Foxn1 hair shaft differentiation hair keratin genes keratinocyte differentiation terminal differentiation markers nail dystrophy hair follicles nail matrices hair differentiation keratin genes nail disorders hair roots nail beds

Studysummary This study suggests a regulatory model where HOXC13 activates Foxn1, affecting hair and nail differentiation, supported by similarities in Hoxc13(tm1Mrc) and Foxn1(nu) mice phenotypes and gene expression patterns.

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The study investigated the role of the Foxn1 gene in hair follicle and nail differentiation, identifying it as a regulatory target of the HOXC13 gene. It demonstrated that HOXC13 directly activated Foxn1, which is crucial for proper hair and nail development. Mutations in these genes led to defects in hair shaft organization and nail structure, as seen in Hoxc13 null and Foxn1nu (nude) mutant mice. The research highlighted the genetic interactions necessary for keratinocyte differentiation, contributing to the understanding of conditions like alopecia and nail dystrophies. Techniques such as DNA microarray analysis, co-transfection assays, and chromatin immunoprecipitation were used to confirm these findings.

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research Desmoglein 4 Is Regulated by Transcription Factors Implicated in Hair Shaft Differentiation

35 citations , August 2009 in “Differentiation”

This study found that transcription factors HOXC13, LEF1, and FOXN1 repress DSG4 transcription, with the Notch pathway possibly involved in maintaining DSG4 expression in hair follicles.

research Genetic Interplays Between Msx2 And Foxn1 Are Required For Notch1 Expression And Hair Shaft Differentiation

67 citations , December 2008 in “Developmental Biology”

This study found that the transcription factors Msx2 and Foxn1 are crucial for maintaining Notch1 expression in the hair follicle matrix, which is necessary for proper hair differentiation.

research Smad4-Dependent Desmoglein-4 Expression Contributes to Hair Follicle Integrity

28 citations , July 2008 in “Developmental Biology”

This study found that the loss of Smad4 in keratinocytes reduces Dsg4 expression via disrupted BMP signaling, contributing to hair follicle degeneration and alopecia.

Evidence That the Satin Hair Mutant Gene Foxq1 Is Among Multiple and Functionally Diverse Regulatory Targets for Hoxc13 During Hair Follicle Differentiation

research Evidence That the Satin Hair Mutant Gene Foxq1 Is Among Multiple and Functionally Diverse Regulatory Targets for Hoxc13 During Hair Follicle Differentiation

65 citations , July 2006 in “Journal of biological chemistry/The Journal of biological chemistry”

This study found that overexpression of Hoxc13 in GC13 mouse models affects hair follicle differentiation by interacting with medulla-specific genes, particularly Foxq1, suggesting a regulatory pathway for medulla differentiation.

research The HOXC13-Controlled Expression of Early Hair Keratin Genes in the Human Hair Follicle Does Not Involve TALE Proteins MEIS and PREP as Cofactors

18 citations , November 2005 in “Archives of Dermatological Research”

research Learning From Nudity: Lessons From The Nude Phenotype

86 citations , October 2005 in “Experimental Dermatology”

This review explores the role of Foxn1 in mammalian skin biology, discussing its influence on hair follicle function and the potential for further research to enhance understanding of epithelial differentiation.

research Keratins of the Human Hair Follicle

276 citations , January 2005 in “International review of cytology”

More research is needed to understand how hair keratins work and their role in hair disorders.

research FOXN1 Is Critical for Onycholemmal Terminal Differentiation in Nude (Foxn1nu) Mice

58 citations , November 2004 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study found that mutations in the Foxn1 gene in nude mice affect not only hair but also nail structure and differentiation, offering insights into nail hypergranulosis pathogenesis relevant to human nail diseases.

research Krtap16: Characterization of a New Hair Keratin-Associated Protein Gene Complex on Mouse Chromosome 16 and Evidence for Regulation by Hoxc13

47 citations , September 2004 in “Journal of Biological Chemistry”

This study provides evidence supporting a regulatory relationship between the transcriptional regulator Hoxc13 and Krtap16 genes, which are crucial for proper hair growth in mice.

research Hox in Hair Growth and Development

98 citations , April 2003 in “Die Naturwissenschaften”

research HOXC13 Is Involved in the Regulation of Human Hair Keratin Gene Expression

132 citations , February 2002 in “Journal of Biological Chemistry”

This study demonstrated that HOXC13 directly influences hair keratin gene expression by binding to specific DNA motifs, suggesting its role in early hair follicle differentiation.

research Molecular Mechanisms Regulating Hair Follicle Development

854 citations , February 2002 in “The journal of investigative dermatology/Journal of investigative dermatology”

This review summarizes recent advances in understanding the molecular mechanisms of hair follicle formation and discusses potential future clinical applications for treating hair loss and skin tumors, but it reports no new clinical results.

research The Nude Gene and the Skin

41 citations , October 2001 in “Experimental Dermatology”

This review discusses the molecular and functional aspects of the nude gene in skin biology, providing insights into its role and evolutionary development, but reports no new results.

research Overexpression of Hoxc13 in Differentiating Keratinocytes Results in Downregulation of a Novel Hair Keratin Gene Cluster and Alopecia

114 citations , May 2001 in “Development”

This study found that overexpressing the Hoxc13 gene in mice causes hair loss and a skin condition similar to ichthyosis, identifying several gene targets that may regulate hair growth.

research Forkhead/Winged-Helix Transcription Factor Whn Regulates Hair Keratin Gene Expression: Molecular Analysis of the Nude Skin Phenotype

75 citations , April 2000 in “Developmental Dynamics”

This study suggests that the structural integrity and physical proximity of Whn's DNA binding and activation domains are crucial for hair keratin gene activation and may explain the nude phenotype.

research Genetically Separable Determinants of Hair Keratin Gene Expression

27 citations , January 2000 in “Developmental Dynamics”

This study reports that a new nude allele, nu(StL), encodes a truncated Whn transcription factor affecting T-cell development and keratin gene expression, with notable differences from the original Whn(nu) mutation.

research Whn and mHa3 Are Components of the Genetic Hierarchy Controlling Hair Follicle Differentiation

79 citations , December 1999 in “Mechanisms of Development”

Whn is crucial for hair growth in certain areas by controlling a specific gene.

research Hoxc13 Mutant Mice Lack External Hair

245 citations , January 1998 in “Genes & Development”

This study found that Hoxc13 mutations in mice cause defects in hair, nail, and tongue structures, with the most noticeable issue being brittle hair leading to alopecia.