title: Delayed cutaneous wound healing and aberrant expression of hair follicle stem cell markers in mice selectively lacking Ctip2 in epidermis.
abstract: BACKGROUND
  COUP-TF interacting protein 2 [(Ctip2), also known as Bcl11b] is an important regulator of skin homeostasis, and is overexpressed in head and neck cancer. Ctip2(ep-/-) mice, selectively ablated for Ctip2 in epidermal keratinocytes, exhibited impaired terminal differentiation and delayed epidermal permeability barrier (EPB) establishment during development, similar to what was observed in Ctip2 null (Ctip2(-/-)) mice. Considering that as an important role of Ctip2, and the fact that molecular networks which underlie cancer progression partially overlap with those responsible for tissue remodeling, we sought to determine the role of Ctip2 during cutaneous wound healing.
  
  
  RESULTS
  Full thickness excisional wound healing experiments were performed on Ctip2(L2/L2) and Ctip2(ep-/-) animals per time point and used for harvesting samples for histology, immunohistochemistry (IHC) and immunoblotting. Results demonstrated inherent defects in proliferation and migration of Ctip2 lacking keratinocytes during re-epithelialization. Mutant mice exhibited reduced epidermal proliferation, delayed keratinocyte activation, altered cell-cell adhesion and impaired ECM development. Post wounding, Ctip2(ep-/-) mice wounds displayed lack of E-Cadherin suppression in the migratory tongue, insufficient expression of alpha smooth muscle actin (alpha SMA) in the dermis, and robust induction of K8. Importantly, dysregulated expression of several hair follicle (HF) stem cell markers such as K15, NFATc1, CD133, CD34 and Lrig1 was observed in mutant skin during wound repair.
  
  
  CONCLUSIONS
  Results confirm a cell autonomous role of keratinocytic Ctip2 to modulate cell migration, proliferation and/or differentiation, and to maintain HF stem cells during cutaneous wounding. Furthermore, Ctip2 in a non-cell autonomous manner regulated granulation tissue formation and tissue contraction during wound closure.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, United States of America.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Liang
authors.forename: Shreya
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Gaurav
authors.initials: G
authors.lastname: Bajaj
authors.forename: Gunjan
authors.initials: G
authors.lastname: Guha
authors.forename: Zhixing
authors.initials: Z
authors.lastname: Wang
authors.forename: Hyo-Sang
authors.initials: HS
authors.lastname: Jang
authors.forename: Mark
authors.initials: M
authors.lastname: Leid
authors.forename: Arup Kumar
authors.initials: AK
authors.lastname: Indra
authors.forename: Gitali
authors.initials: G
authors.lastname: Ganguli-Indra
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000096:biosynthesis; D002454:Cell Differentiation; D002465:Cell Movement; D018450:Disease Progression; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000378:metabolism*; D007150:Immunohistochemistry / Q000379:methods; D015603:Keratinocytes / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010590:Phalloidine / Q000096:biosynthesis; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism*; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology; D014212:Tretinoin / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D000199:Actins; C511143:Bcl11b protein, mouse; D015820:Cadherins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D010590:Phalloidine; D014212:Tretinoin