Sequences 5′ of the bovine keratin 5 gene direct tissue- and cell-type-specific expression of a lacZ gene in the adult and during development

Ramı́rez, Ángel; Bravo, Ana; Jorcano, José L.; Vidal, Miguel

doi:10.1046/j.1432-0436.1994.5810053.x

Cited by 153 publications

(192 citation statements)

References 47 publications

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“…30,31 Gli proteins mediate transcriptional responses to Hedgehog family members, 19,20 and the Gli2⌬C4 transactivation-domain mutant blocks Gli func-tion in a dominant-negative manner. 22 To inhibit Hedgehog signaling selectively in cutaneous epithelium, we used the bovine K5 promoter 23 to generate K5-Gli2⌬C4 transgenic mice. The K5 promoter is active in the epidermal basal layer, embryonic hair follicle progenitor cells, and follicle outer root sheath, including the bulge region which harbors multipotent stem cells.…”

Section: Resultsmentioning

confidence: 99%

“…Hiroshi Sasaki and Chi-chung Hui) with ApaI, adding a fragment containing a stop codon flanked by ApaI sites, and re-ligating. Gli2⌬C4 cDNA was released from pcDNA3.1 using PmeI, and subcloned into the SnaBI site of the bovine K5 cassette 23 to generate K5-Gli2⌬C4. All subcloning was verified by sequencing.…”

Section: Construction and Breeding Of Transgenic Micementioning

confidence: 99%

“…We modified the K5 transgenic cassette 23 to enable Cre-mediated expression of M2SMO, which encodes a constitutively activated form of the hedgehog signaling effector SMO, 24 in skin. A fragment containing an EGFP cDNA with bovine growth hormone polyA signal, flanked by loxP sites in reverse orientation, was inserted into the NotI site of the K5 transgenic cassette.…”

Section: Construction and Breeding Of Transgenic Micementioning

confidence: 99%

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Hedgehog Signaling Regulates Sebaceous Gland Development

Allen

Grachtchouk

Sheng

et al. 2003

The American Journal of Pathology

115

104

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Epithelial progenitor cells in skin give rise to multiple lineages, comprising the hair follicle, an associated sebaceous gland, and overlying epidermis; however, the signals that regulate sebocyte development are poorly understood. We tested the potential involvement of the Hedgehog pathway in sebaceous gland development using transgenes designed to either block or stimulate Hedgehog signaling in cutaneous keratinocytes in vivo. Whereas inhibition of the Hedgehog pathway selectively suppressed sebocyte development, Hedgehog pathway activation led to a striking increase both in size and number of sebaceous glands. Remarkably, ectopic Hedgehog signaling also triggered the formation of sebaceous glands from footpad epidermis, in regions normally devoid of hair follicles and associated structures. These ectopic sebaceous glands expressed molecular markers of sebocyte differentiation and were functional, secreting their contents directly onto the skin's surface instead of into a hair canal. The Hedgehog pathway thus plays a key role in sebocyte cell fate decisions and is a potential target for treatment of skin disorders linked to abnormal sebaceous gland function, such as acne.

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Section: Resultsmentioning

confidence: 99%

Section: Construction and Breeding Of Transgenic Micementioning

confidence: 99%

Section: Construction and Breeding Of Transgenic Micementioning

confidence: 99%

See 1 more Smart Citation

Hedgehog Signaling Regulates Sebaceous Gland Development

Allen

Grachtchouk

Sheng

et al. 2003

The American Journal of Pathology

115

104

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“…The expression of murine cyclin D3 was targeted to stratified epithelial by the bovine keratin 5 gene as previously described (Ramirez et al, 1994;RodriguezPuebla et al, 2000). As expected, cyclin D3 protein levels increased 30-fold when compared with normal sibling mice (Figure 1a, lanes 1 and 3).…”

Section: Molecular Analysis Of Keratinocytes Overexpressing Cyclin D3mentioning

confidence: 99%

Cyclin D2 and cyclin D3 play opposite roles in mouse skin carcinogenesis

Rojas¹,

Cadenas

Lin

et al. 2006

Oncogene

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D-type cyclins are components of the cell-cycle engine that link cell signaling pathways and passage throughout G1 phase. We previously described the effects of overexpression cyclin D1, D2 or D3 in mouse epidermis and tumor development. We now asked whether cyclin D2 and/or cyclin D3 play a relevant role in ras-dependent tumorigenesis. Here, we described the effect of cyclin D3 and cyclin D2 overexpression in mouse skin tumor development. Notably, overexpression of cyclin D3 results in reduced tumor development and malignant progression to squamous cell carcinomas (SCC). Biochemical analysis of keratinocytes shows that overexpression of cyclin D3 results in strong reduction of cyclin D2 and its associated kinase activity. Furthermore, we found that reinstatement of cyclin D2 level in the cyclin D3/cyclin D2 bigenic mice results in a complete reversion of the inhibitory action of cyclin D3. Supporting these results, ablation of cyclin D2 results in reduced tumorigenesis and malignant progression. On the other hand, overexpression of cyclin D2 results in an increased number of papillomas and malignant progression. We conclude that cyclin D3 and cyclin D2 play opposite roles in mouse skin tumor development and that the suppressive activity of cyclin D3 is associated with cyclin D2 downregulation.

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“…Therefore, this system provides a useful tool for inactivating genes in the epidermis and hair follicles at specific stages of development. (Kellendonk et al, 1996) was inserted into the K5 targeting vector which contains a 5.2 kb bovine K5 promoter, a human ␤-globin intron, and a 1.2 kb SV40 polyadenylation signal (Ramirez et al, 1994). The K5.CrePR1 transgene was microinjected into mouse embryos obtained from mating ICR females to strain FVB males and maintained in the ICR background.…”

mentioning

confidence: 99%