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(American Journal of Pathology. 2003;163:2173-2178.)
© 2003 American Society for Investigative Pathology

Short Communication

Hedgehog Signaling Regulates Sebaceous Gland Development

Mary Allen^*, Marina Grachtchouk^*, Hong Sheng^*, Vladimir Grachtchouk^*, Anna Wang^*, Lebing Wei^*, Jianhong Liu^*, Angel Ramirez, Daniel Metzger, Pierre Chambon, Jose Jorcano and Andrzej A. Dlugosz^*

From the Department of Dermatology and Comprehensive Cancer Center,^* University of Michigan, Ann Arbor, Michigan; Project on Cell and Molecular Biology and Gene Therapy, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain; and Institut de Genetique et de Biologie Moleculaire et Cellulaire, College de France, Communaute Urbaine de Strasbourg, Strasbourg, France

Epithelial progenitor cells in skin give rise to multiple lineages, comprising the hair follicle, an associated sebaceous gland, and overlying epidermis; however, the signals that regulate sebocyte development are poorly understood. We tested the potential involvement of the Hedgehog pathway in sebaceous gland development using transgenes designed to either block or stimulate Hedgehog signaling in cutaneous keratinocytes in vivo. Whereas inhibition of the Hedgehog pathway selectively suppressed sebocyte development, Hedgehog pathway activation led to a striking increase both in size and number of sebaceous glands. Remarkably, ectopic Hedgehog signaling also triggered the formation of sebaceous glands from footpad epidermis, in regions normally devoid of hair follicles and associated structures. These ectopic sebaceous glands expressed molecular markers of sebocyte differentiation and were functional, secreting their contents directly onto the skin’s surface instead of into a hair canal. The Hedgehog pathway thus plays a key role in sebocyte cell fate decisions and is a potential target for treatment of skin disorders linked to abnormal sebaceous gland function, such as acne.

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