A group of scientists led by Dr. Elaine Fuchs at the Howard Hughes Medical Institute at the Rockefeller University have uncovered an unexpected new role for the well-known transcription factor, GATA-3, in hair follicle development. GATA-3 was previously identified for its role in coaxing hematopoietic stem cells towards a T-cell fate. Now, Dr. Fuchs and colleagues reveal that GATA-3 is also involved in epidermal stem cell specification. This finding lends valuable insight into hair follicle generation, and highlights intriguing parallels between the molecular cues that direct cell fate specification in the skin and the immune system.

Each of the roughly 5 million hair follicles that cover the adult human body has a similar structure. The hair follicle consists of a multi-layered hair shaft, the outermost layer of which is referred to as the cuticle. Below the skin surface, the cuticle is surrounded by an inner root sheath (IRS).

"The IRS acts as a channel, functioning to guide the developing hair shaft up to the skin surface. Without the channel, the hair does not develop properly," explains professor Fuchs.

In an effort to understand how cells are directed towards an IRS fate, Dr. Fuchs and two MD/PhD students, Charles Kaufman and Diana Bolotin, used microarray analysis to monitor gene expression levels in the dorsal (back) skin of embryonic mice. GATA-3 emerged as one gene that was turned on during hair morphogenesis. Further work by Dr. Fuchs and colleagues revealed that the GATA-3 protein is specifically expressed in IRS cells of the hair follicle.

These findings, coupled with existing knowledge of GATA-3's function as a master gene regulator of cell lineage specification in the immune system, posited GATA-3 as an attractive candidate for directing epidermal stem cells to become IRS cells.

To investigate the precise role of GATA-3 in hair follicle morphogenesis, Dr. Fuchs and colleagues turned to a strain of GATA-3-de
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Contact: Heather Cosel
coselpie@cshl.org
Cold Spring Harbor Laboratory
21-Aug-2003

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