High commitment of embryonic keratinocytes to terminal differentiation through a Notch1-caspase 3 regulatory mechanism.
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.
Okuyama
Ryuhei
R
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Nguyen
Bach-Cuc
BC
Talora
Claudio
C
Ogawa
Eisaku
E
Tommasi di Vignano
Alice
A
Lioumi
Maria
M
Chiorino
Giovanna
G
Tagami
Hachiro
H
Woo
Minna
M
Dotto
G Paolo
GP
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
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