title: Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130.
abstract: The functions of p107 and p130, members of the retinoblastoma family, include the control of cell cycle progression and differentiation in several tissues. Our previous studies suggested a role for p107 and p130 in keratinocyte differentiation in vitro. We now extend these data using knockout animal models. We found impaired terminal differentiation in the interfollicular keratinocytes of p107/p130-double-null mice epidermis. In addition, we observed a decreased number of hair follicles and a clear developmental delay in hair, whiskers and tooth germs. Skin grafts of p107/p130-deficient epidermis onto NOD/scid mice showed altered differentiation and hyperproliferation of the interfollicular keratinocytes, thus demonstrating that the absence of p107 and p130 results in the deficient control of differentiation in keratinocytes in a cell-autonomous manner. Besides normal hair formation, follicular cysts, misoriented and dysplastic follicles, together with aberrant hair cycling, were also observed in the p107/p130 skin transplants. Finally, the hair abnormalities in p107/p130-null skin were associated with altered Bmp4-dependent signaling including decreased DeltaNp63 expression. These results indicate an essential role for p107 and p130 in the epithelial-mesenchimal interactions.
authors.affiliation: Program on Cell and Molecular Biology and Gene Therapy. CIEMAT, Avenue Complutense 22, E28040 Madrid, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Ruiz
authors.forename: Carmen
authors.initials: C
authors.lastname: Segrelles
authors.forename: Ana
authors.initials: A
authors.lastname: Bravo
authors.forename: Mirentxu
authors.initials: M
authors.lastname: Santos
authors.forename: Paloma
authors.initials: P
authors.lastname: Perez
authors.forename: Hugo
authors.initials: H
authors.lastname: Leis
authors.forename: Jose L
authors.initials: JL
authors.lastname: Jorcano
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Paramio
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000235:genetics; D004817:Epidermis / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D018859:Hair Follicle / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011506:Proteins; D016160:Retinoblastoma Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; D015398:Signal Transduction; D012868:Skin Abnormalities / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016038:Skin Transplantation; D014083:Tooth Germ / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; C489485:Rbl1 protein, mouse; C493838:Rbl2 protein, mouse; D016160:Retinoblastoma Protein; D050720:Retinoblastoma-Like Protein p107; D050717:Retinoblastoma-Like Protein p130; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C486419:Trp63 protein, mouse; D025521:Tumor Suppressor Proteins