title: High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism.
abstract: Embryonic cells are expected to possess high growth/differentiation potential, required for organ morphogenesis and expansion during development. However, little is known about the intrinsic properties of embryonic epithelial cells due to difficulties in their isolation and cultivation. We report here that pure keratinocyte populations from E15.5 mouse embryos commit irreversibly to differentiation much earlier than newborn cells. Notch signaling, which promotes keratinocyte differentiation, is upregulated in embryonic keratinocyte and epidermis, and elevated caspase 3 expression, which we identify as a transcriptional Notch1 target, accounts in part for the high commitment of embryonic keratinocytes to terminal differentiation. In vivo, lack of caspase 3 results in increased proliferation and decreased differentiation of interfollicular embryonic keratinocytes, together with decreased activation of PKC-delta, a caspase 3 substrate which functions as a positive regulator of keratinocyte differentiation. Thus, a Notch1-caspase 3 regulatory mechanism underlies the intrinsically high commitment of embryonic keratinocytes to terminal differentiation.
authors.affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Okuyama
authors.forename: Bach-Cuc
authors.initials: BC
authors.lastname: Nguyen
authors.forename: Claudio
authors.initials: C
authors.lastname: Talora
authors.forename: Eisaku
authors.initials: E
authors.lastname: Ogawa
authors.forename: Alice
authors.initials: A
authors.lastname: Tommasi di Vignano
authors.forename: Maria
authors.initials: M
authors.lastname: Lioumi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Chiorino
authors.forename: Hachiro
authors.initials: H
authors.lastname: Tagami
authors.forename: Minna
authors.initials: M
authors.lastname: Woo
authors.forename: G Paolo
authors.initials: GP
authors.lastname: Dotto
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000196:embryology* / Q000254:growth & development*; D005333:Fetus; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D051745:Protein Kinase C-delta; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors; D015854:Up-Regulation / Q000235:genetics
chemical_list: C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D014157:Transcription Factors; C497259:Prkcd protein, mouse; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases