Epidermal and craniofacial defects in mice overexpressing Klf5 in the basal layer of the epidermis.
Krüppel-like factor5 (Klf5) is a zinc-finger transcription factor normally expressed in the skin. Here, we show that overexpression of Klf5 in the basal layer of the epidermis during embryogenesis affects epidermal development and disrupts epithelial-mesenchymal interactions necessary for skin adnexae formation as well as craniofacial morphogenesis. The transgenic mice exhibited exencephaly, craniofacial defects, persistent abdominal herniation and ectodermal dysplasia. Moreover, the epidermis was hypoplastic and underwent abnormal differentiation with expression of keratin8, a marker for single-layered epithelia, in the stratified epidermis. Correspondingly, we observed a downregulation of DeltaNp63 expression in the skin. Overexpression of Klf5 in adult mice led to hyperkeratosis, follicle occlusion and epidermal erosions. Further, we observed decrease and even loss of the stem cell population of bulge keratinocytes, as characterized by the expression pattern of alpha6 integrin and CD34 markers. Our data suggest a new role of Klf5 as a modulator of p63 expression and the differentiation program of epidermal cells relevant for regenerative potential of the epidermis and epithelial-mesenchymal interactions.
Sur
Inderpreet
I
Department of Bioscience and Nutrition, Clinical Research Center, and Department of Laboratory Medicine Division of Pathology, Karolinska Institutet, Novum, SE-141 57 Huddinge, Sweden. inderpreet.sur@cnt.ki.se
Rozell
Björn
B
Jaks
Viljar
V
Bergström
Asa
A
Toftgård
Rune
R
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D019465:Craniofacial Abnormalities; D004476:Ectodermal Dysplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000078404:Epidermal Cells; D004817:Epidermis / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D005260:Female; D006801:Humans; D053533:Keratin-8 / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D016335:Zinc Fingers
D018952:Antigens, CD34; D015415:Biomarkers; D053533:Keratin-8; C118391:Klf5 protein, mouse; C486595:Krt8 protein, mouse; D051741:Kruppel-Like Transcription Factors; D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse