Notch signalling is linked to epidermal cell differentiation level in basal cell carcinoma, psoriasis and wound healing.
BACKGROUND
Epidermal homeostasis involves the monitoring of continuous proliferative and differentiative processes as keratinocytes migrate from the basal layer to the skin surface. Recently, differentiation of epidermal stem cells was shown to be promoted by the Notch pathway. This pathway is characterised by cell-cell interactions between transmembrane proteins and was first implicated in lateral inhibition, patterning and cell binary choices during embryogenesis.


METHODS
By in situ hybridisation, we investigated the in vivo expression of related genes, namely; Notch 1-3, Delta 1, Jagged 1, Lunatic Fringe, Radical Fringe and Manic Fringe during keratinocyte proliferation and differentiation in humans in basal cell carcinoma, psoriasis and in wound healing experiments, compared with normal adult skin.


RESULTS
We show that the highest level of transcription of these genes is in the basal cell layer of non-lesional skin. Conversely, when keratinocytes were hyperproliferating, as in basal cell carcinoma, psoriasis, and during the first step of re-epithelialisation, expression was weak or non-existent. Furthermore, normal levels of transcripts were rescued in psoriatic plaques when treated by phototherapy, as well as in newly regenerated stratified epidermis following wound healing.


CONCLUSIONS
The Notch signalling involved in the differentiation programme of normal adult human epidermis is altered under experimental conditions and pathologies which modify this programme.
Thélu
Jacques
J
LEDAC, CNRS 5538, Institut A, Bonniot, Université J, Fourier, Grenoble, France. jacques.thelu@ujf-grenoble.fr
Rossio
Patricia
P
Favier
Bertrand
B
D000328:Adult; D000818:Animals; D001483:Base Sequence; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics; D029721:Drosophila Proteins; D006801:Humans; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D011565:Psoriasis / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D051880:Receptors, Notch; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms; D016038:Skin Transplantation / Q000502:physiology; D013234:Stem Cells / Q000473:pathology; D014158:Transcription, Genetic; D015854:Up-Regulation; D014945:Wound Healing / Q000235:genetics*
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; C064045:delta protein; D017351:N-Acetylglucosaminyltransferases; C090576:fng protein, Drosophila