Born in a follicle--a historical perspective.

A review of major studies of tetrapod skin development since the 1870s illustrates how knowledge of structure and mechanism progressed through phases emphasizing Natural History, morphology, endocrinology, and tissue manipulation prior to the prevailing "molecular era." Each successive phase of investigation, while suffering from its own limitations and constraints, has produced conceptual advances. At various times, different systems in various organisms have been research models of choice for practical and/or technical reasons. Comparative studies of scaled and non-scaled integuments and appendages thereof, e.g., nails, claws, glands, hair, and especially feathers, revealed data that suggested new directions for research programs. Some non-mammalian models still offer unique opportunities for pursuit of specific questions pertinent to studies of hair: arguments between American and British schools concerning feather development that originated in the 1930s remain unresolved and may thus affect interpretation of recent investigations. The current emphasis on the study of diffusible molecules involved in papilla-follicle interactions in hair development and replacement can only be understood in the context of the interwoven history of questions relating sequentially to evolutionary homology, physiological controls of tissue homeostasis, embryonic induction, and, most recently, molecular genetics.