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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Cell Division
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DNA-Binding Proteins / genetics
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Epidermis / abnormalities
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Epidermis / metabolism
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Epidermis / pathology
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Epithelium / abnormalities
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Epithelium / metabolism
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Epithelium / pathology
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Gene Expression
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Genes, Tumor Suppressor
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Hair Follicle / abnormalities
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Hair Follicle / metabolism
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Hair Follicle / pathology
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Keratinocytes / metabolism
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Keratinocytes / pathology
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Mesoderm / metabolism
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Mesoderm / pathology
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Mice
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Mice, Inbred NOD
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Mice, Knockout
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Mice, SCID
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Nuclear Proteins / deficiency
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Phosphoproteins / deficiency
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Phosphoproteins / genetics
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Phosphoproteins / physiology*
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Proteins*
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Retinoblastoma Protein / deficiency
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Retinoblastoma Protein / genetics
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Retinoblastoma Protein / physiology*
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Retinoblastoma-Like Protein p107
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Retinoblastoma-Like Protein p130
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Signal Transduction
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Skin Abnormalities / genetics
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Skin Abnormalities / metabolism
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Skin Abnormalities / pathology*
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Skin Transplantation
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Tooth Germ / abnormalities
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Tooth Germ / metabolism
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Tooth Germ / pathology
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Trans-Activators*
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Transcription Factors
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Tumor Suppressor Proteins
Substances
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DNA-Binding Proteins
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Nuclear Proteins
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Phosphoproteins
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Proteins
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Rbl1 protein, mouse
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Rbl2 protein, mouse
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Retinoblastoma Protein
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Retinoblastoma-Like Protein p107
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Retinoblastoma-Like Protein p130
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TP63 protein, human
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Trans-Activators
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Transcription Factors
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Trp63 protein, mouse
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Tumor Suppressor Proteins