The epidermis is continually shed and replenished throughout life. Maintenance of the epidermis is dependent on a stem cell population found in the basal layer of the epidermis. These stem cells self-renew and contribute progenitors called transit amplifying cells. Stem cells and the subsequent transit amplifying cells contribute to multiple lineages of terminally differentiated cells including hair follicle cells, sebocytes, and interfollicular epidermal cells. Although it is clear that epidermal stem cells contribute to all three lineages, the role of transit amplifying cells in lineage commitment remains unknown and largely uninvestigated. The purpose of this proposal is to use in vitro and in vivo methods to investigate if transit amplifying cells contribute to one or multiple lineages. Specifically, the aims are to determine if human neonatal foreskin cultures can make sebocytes and hair follicle proteins, and to use this system to investigate the lineages that develop from a single transit amplifying cell. Additionally, the role of c-Myc and 13-catenin in lineage commitment of transit amplifying cells will be investigated, and using the BOLAP retroviral library, the fate of transit amplifying cells in vivo will be mapped. The process of stem cell maturation is essential to maintain the skin, and disruptions in the stem cell differentiation process have pathological implications in cancer, psoriasis, acne, and hair loss.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AR049651-03X1
Application #
7179194
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Baker, Carl
Project Start
2003-12-01
Project End
2007-07-16
Budget Start
2006-03-17
Budget End
2007-07-16
Support Year
3
Fiscal Year
2006
Total Cost
$7,000
Indirect Cost
Name
Cancer Research United Kingdom
Department
Type
DUNS #
423375711
City
London
State
Country
United Kingdom
Zip Code
EC1 -4AD
Ambler, Carrie A; Watt, Fiona M (2010) Adult epidermal Notch activity induces dermal accumulation of T cells and neural crest derivatives through upregulation of jagged 1. Development 137:3569-79
Watt, Fiona M; Estrach, Soline; Ambler, Carrie A (2008) Epidermal Notch signalling: differentiation, cancer and adhesion. Curr Opin Cell Biol 20:171-9
Ambler, Carrie A; Watt, Fiona M (2007) Expression of Notch pathway genes in mammalian epidermis and modulation by beta-catenin. Dev Dyn 236:1595-601
Estrach, Soline; Ambler, Carrie A; Lo Celso, Cristina et al. (2006) Jagged 1 is a beta-catenin target gene required for ectopic hair follicle formation in adult epidermis. Development 133:4427-38