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Curr Biol 2003 Feb 18;13(4):333-8
Notch/RBP-J Signaling Regulates Epidermis/Hair Fate Determination of Hair Follicular Stem Cells.
Notch signaling is involved in the cell fate determination of various cell lineages. Notch interaction with its ligand induces the cleavage of its intracellular domain (IC), and the Notch IC translocates to the nucleus and binds to RBP-J to transactivate transcription of target genes. All four Notches in mammals bind to RBP-J to exert their transactivation activities. Notch is expressed in developing or differentiating epidermis and hairs, inhibits the terminal differentiation of the epidermis, and regulates hair differentiation. The common stem cells that reside in the upper portion of hair follicles (the bulge) contribute to epidermal and hair cell formation. However, it is unknown what determines whether hair follicular stem cells will become hairs or epidermis. Here we report that conditionally disrupting the mouse RBP-J gene in a mosaic pattern to avoid embryonic lethality of RBP-J-deficiency caused hair loss, epidermal hyperkeratinization, and epidermal cyst formation. Cyst formation is probably due to a combination of the aberrant fate determination of RBP-J-deficient stem cells to epidermal progenitors and their accelerated differentiation into epidermis. These results suggest that Notch/RBP-J signaling regulates the cell fate determination of hair follicular stem cells at the bulge region.
Genomics 2003 Jan;81(1):6-14
Curly bare (cub), a new mouse mutation on chromosome 11 causing skin and hair abnormalities, and a modifier gene (mcub) on chromosome 5.
In the outcrossing of a new recessive mouse mutation causing hair loss, a new wavy-coated phenotype appeared. The two distinct phenotypes were shown to be alternative manifestations of the same gene mutation and attributable to a single modifier locus. The new mutation, curly bare (cub), was mapped to distal Chr 11 and the modifier (mcub) was mapped to Chr 5. When homozygous for the recessive mcub allele, cub/cub mice appear hairless. A single copy of the dominant Mcub allele confers a full, curly coat in cub/cub mice. Reciprocal transfer of full-thickness skin grafts between mutant and control animals showed that the skin phenotype was tissue autonomous. The hairless cub/cub mcub/mcub mice show normal contact sensitivity responses to oxazolone. The similarity of the wavy coat phenotype to those of Tgfa and Egfr mutations and the map positions of cub and mcub suggest candidate genes that interact in the EGF receptor signal transduction pathway.
Dermatol Surg 2002 Oct;28(10):894-900; discussion 900
The potential role of minoxidil in the hair transplantation setting.
BACKGROUND: Over the last decade surgical management of hair loss has become an increasingly popular and satisfying procedure for both men and women, as innovations in donor harvesting, graft size, and hairline design have resulted in consistently natural-appearing hair restoration. OBJECTIVE: In addition, a better understanding of the regulation of the hair-growth cycle has led to advances in the pharmacologic treatment of androgenetic alopecia. METHODS: Currently there are two U.S. Food and Drug Administration (FDA)-approved agents that promote hair regrowth: over-the-counter topical minoxidil solution for men and women and prescription oral finasteride tablets for men. In October 2001, a group of 11 international experts on hair loss and hair transplantation convened to review the physiology and effects of pharmacologic treatments of hair loss and to discuss the value of administering topical minoxidil therapy as an adjunct to hair transplantation. RESULTS: This article presents the key findings and consensus points among the participants, including their current use of pharmacologic treatments, strategies for optimal results both pre- and postsurgery, and the importance of realistic patient expectations and compliance. CONCLUSIONS: Based on the surgeons' clinical experience, the use of approved hair regrowth agents in hair transplant patients with viable but suboptimally functioning follicles in the region to be transplanted can increase hair density, speed regrowth in transplanted follicles, and complement the surgical result by slowing down or stopping further hair loss.
J Am Acad Dermatol 2001 Sep;45(3 Suppl):S81-6
Possible mechanisms of miniaturization during androgenetic alopecia or pattern hair loss.
In androgenetic alopecia, or pattern hair loss, follicles undergo miniaturization, shrinking from terminal to vellus-like hairs. Traditionally, this process is thought to progress gradually over a number of follicular cycles. However, it is unlikely that miniaturization can be explained only by a series of progressively shorter anagen cycles. Simple calculations show that this process would take too long for significant miniaturization to occur secondary to shorter anagen cycles alone, especially in view of the latent lag period seen in pattern hair loss that occurs between the loss of a telogen hair and the appearance of an anagen hair. Evidence is presented to support a new concept that miniaturization is an abrupt, large-step process that also can be reversed in 1 hair cycle, as has been shown clinically, with confirmatory histologic evidence, in patients with pattern hair loss responding to finasteride treatment. It is hypothesized that the miniaturization seen with pattern hair loss may be the direct result of reduction in the cell number and, hence, size of the dermal papilla.
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