Dual role of COUP-TF-interacting protein 2 in epidermal homeostasis and permeability barrier formation.
COUP-TF-interacting protein 2 (CTIP2; also known as Bcl11b) is a transcription factor that plays key roles in the development of the central nervous and immune systems. CTIP2 is also highly expressed in the developing epidermis, and at lower levels in the dermis and in adult skin. Analyses of mice harboring a germline deletion of CTIP2 revealed that the protein plays critical roles in skin during development, particularly in keratinocyte proliferation and late differentiation events, as well as in the development of the epidermal permeability barrier. At the core of all of these actions is a relatively large network of genes, described herein, that is regulated directly or indirectly by CTIP2. The analysis of conditionally null mice, in which expression of CTIP2 was ablated specifically in epidermal keratinocytes, suggests that CTIP2 functions in both cell and non-cell autonomous contexts to exert regulatory influence over multiple phases of skin development, including barrier establishment. Considered together, our results suggest that CTIP2 functions as a top-level regulator of skin morphogenesis.
Golonzhka
Olga
O
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97331, USA.
Liang
Xiaobo
X
Messaddeq
Nadia
N
Bornert
Jean-Marc
JM
Campbell
Adam L
AL
Metzger
Daniel
D
Chambon
Pierre
P
Ganguli-Indra
Gitali
G
Leid
Mark
M
Indra
Arup K
AK
D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000502:physiology*; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D005838:Genotype; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D008957:Models, Genetic; D010539:Permeability; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000502:physiology*; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000502:physiology*
C511143:Bcl11b protein, mouse; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins