Hair-Specific Keratins: Characterization and Expression of a Mouse Type I Keratin Gene

Kaytes, Paul S.; McNab, Alistair R.; Rea, Thomas J.; Groppi, Vincent E.; Kawabe, Thomas T.; Buhl, Allen E.; Bertolino, Arthur P.; Hatzenbuhler, Nicole T.; Vögeli, Gabriel

doi:10.1111/1523-1747.ep12491511

Cited by 26 publications

(15 citation statements)

References 36 publications

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“…1 Cortical expression has also been demonstrated for the murine orthologs mHa1, mHa3, and mHa4 (28,29,33). Thus these hair keratins are obviously involved in the late phase of terminal differentiation of the hair fiber.…”

Section: Discussionmentioning

confidence: 95%

Characterization of a 190-Kilobase Pair Domain of Human Type I Hair Keratin Genes

Rogers

Winter

Wolf

et al. 1998

Journal of Biological Chemistry

118

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Polymerase chain reaction-based screening of an arrayed human P1 artificial chromosome (PAC) library using primer pairs specific for the human type I hair keratins hHa3-II or hHa6, led to the isolation of two PAC clones, which covered 190 kilobase pairs (kbp) of genomic DNA and contained nine human type I hair keratin genes, one transcribed hair keratin pseudogene, as well as one orphan exon. The hair keratin genes are 4 -7 kbp in size, exhibit intergenic distances of 5-8 kbp, and display the same direction of transcription. With one exception, all hair keratin genes are organized into 7 exons and 6 positionally conserved introns. On the basis of sequence homologies, the genes can be grouped into three subclusters of tandemly arranged genes. One subcluster harbors the highly related genes hHa1, hHa3-I, hHa3-II, and hHa4. A second subcluster of highly related genes comprises the novel genes hHa7 and hHa8, as well as pseudogene ⌿hHaA, while the structurally less related genes hHa6, hHa5, and hHa2 are constituents of the third subcluster. As shown by reverse transcription-polymerase chain reaction, all hair keratin genes, including the pseudogene, are expressed in the human hair follicle. The transcribed pseudogene ⌿hHaA contains a premature stop codon in exon 4 and exhibits aberrant pre-mRNA splicing. Evolutionary tree construction reveals an early divergence of hair keratin genes from cytokeratin genes, followed by the segregation of the genes into the three subclusters. We suspect that the 190-kbp domain contains the entire complement of human type I hair keratin genes.The keratin multigene family comprises the cytokeratins or soft ␣-keratins, which are expressed in the various types of epithelia, and the hair keratins or hard ␣-keratins, involved in the formation of hard keratinized structures. Both can be divided into type I (acidic) and type II (basic-neutral) proteins that form the 10-nm intermediate filament network of epithelial cells by obligatory association of equimolar amounts of type I and type II keratins (1, 2). Disturbances of intermediate filament formation through deleterious mutations in keratins can lead to a weakening of the structural integrity of the respective epithelial cells, resulting in hereditary disorders of skin, mucosa, nail, or hair (3-7). Although initial studies of hair keratin proteins of several species indicated the existence of eight major type hair keratins, four type I members, termed Ha1-Ha4, and four type II members, termed Hb1-Hb4, as well as of one minor hair keratin pair, Hax/Hbx (8 -11), it has recently been shown that the hair keratin family is distinctly more complex. In man, sequences of seven type I hair keratins, hHa1, hHa2, hHa3-I, hHa3-II, hHa4, 1 hHa5, hHa6 (previously designated hHRa1) 1 and four type II hair keratins, hHb1, hHb3, hHb5, and hHb6, have been elucidated by molecular cloning, and their differential expression in the hair matrix, cortex, and cuticle of the hair follicle has been shown (12-17). To date, complete sequences for one human type I and t...

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Section: Discussionmentioning

confidence: 95%

Characterization of a 190-Kilobase Pair Domain of Human Type I Hair Keratin Genes

Rogers

Winter

Wolf

et al. 1998

Journal of Biological Chemistry

118

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“…Interestingly, for all these genes, the first such motif is positioned similarly, 160-300 bp 5' from the TATA box. In one case where 3688 bp of mouse hair keratin promoter sequence is known (Kaytes et al 1991 ), there are six putative LEF-1-binding sites, each sharing 100% identity with the core sequence. As is typical of the optimal LEF-l-binding site (Giese et al 1992;Giese and Grosschedl 1993), there is often a C preceding the consensus, and A's instead of T's at the 3' end.…”

Section: ' -C T T T G A/t A/t -3'mentioning

confidence: 99%

Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate.

Zhou¹,

Byrne²,

Jacobs³

et al. 1995

Genes Dev.

447

378

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T cell-specific transcription factor (TCF-1) and lymphoid enhancer factor 1 (LEF-1) have been implicated exclusively in the regulation of T cell-specific genes. The only adult tissue other than thymus known to express these factors is spleen and lymph node, which contain low levels of LEF-1 and no TCF-1. We noticed that genes involved in hair-specific gene expression possess LEF-I/TCF-1 consensus motifs located in similar positions relative to their TATA box. We show that of the two factors only LEF-1 is expressed in hair follicles; it can be cloned in both splice forms from human skin keratinocytes and it can bind to these sites in the hair promoters. We show that LEF-1 mRNA is present in pluripotent ectoderm, and it is up-regulated in a highly restricted pattern just before the formation of underlying mesenchymal condensates and commitment of overlying ectodermal cells to invaginate and become hair follicles. New waves of ectodermal LEF-1 spots appear concomitant with new waves of follicle morphogenesis. To test whether LEF-1 patterning might be functionally important for hair patterning and morphogenesis, we used transgenic technology to alter the patterning and timing of LEF-1 over the surface ectoderm. Striking abnormalities arose in the positioning and orientation of hair follicles, leaving a marked disruption of this normally uniform patterning. This provides the first direct evidence that ectodermal cues are critical in establishing these developmental processes, which at later stages are known to be influenced by underlying mesenchyme. Remarkably, elevated LEF-1 in the lip furrow epithelium of developing transgenic animals triggered these cells to invaginate, sometimes leading to the inappropriate adoption of hair follicle and tooth cell fates. Collectively, our findings demonstrate that ectodermal expression of LEF-1 plays a central role in gene expression, pattern formation, and other developmental processes involving epithelial-mesenchymal associations.

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“…The Bmp4 probe con sisted of a 285-bp PstI-£coRI fragment (Wozney et al 1988;Vainio et al 1993), the Msxl probe of a 700-bp £coRI-BgiII fragment (MacKenzie et al 1991). The probe for hair keratin Al was prepared by reverse transcriptase-based PCR and cloning and comprised of nucleotides 1009-1127 (Kaytes et al 1991).…”

Section: In Situ Hybridization and Immunocytochemistrymentioning

confidence: 99%

Lef1 expression is activated by BMP-4 and regulates inductive tissue interactions in tooth and hair development.

Kratochwil

Dull²,

Fariñas³

et al. 1996

Genes Dev.

395

323

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Targeted inactivation of the murine gene encoding the transcription factor LEF-1 abrogates the formation of organs that depend on epithelial-mesenchymal tissue interactions. In this study we have recombined epithelial and mesenchymal tissues from normal and LEF-1-deficient embryos at different stages of development to define the LEF-1-dependent steps in tooth and whisker organogenesis. At the initiation of organ development, formation of the epithelial primordium of the whisker but not tooth is dependent on mesenchymal Left gene expression. Subsequent formation of a whisker and tooth mesenchymal papilla and completion of organogenesis require transient expression of Lefl in the epithelium. These experiments indicate that the effect of Lefl expression is transmitted from one tissue to the other. In addition, the finding that the expression of Lefl can be activated by bone morphogenetic protein 4 (BMP-4) suggests a regulatory role of this transcription factor in BMP-mediated inductive tissue interactions.[Key Words: Lefl; BMP-4; epithelial-mesenchymal interactions; tooth and whisker development]

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Hair-Specific Keratins: Characterization and Expression of a Mouse Type I Keratin Gene

Cited by 26 publications

References 36 publications

Characterization of a 190-Kilobase Pair Domain of Human Type I Hair Keratin Genes

Characterization of a 190-Kilobase Pair Domain of Human Type I Hair Keratin Genes

Lymphoid enhancer factor 1 directs hair follicle patterning and epithelial cell fate.

Lef1 expression is activated by BMP-4 and regulates inductive tissue interactions in tooth and hair development.

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