1. ¹Department of Biochemistry, Vanderbilt University Medical Center, Nashville, Tennessee, USA
2. ²Department of Medicine (Dermatology), Vanderbilt University Medical Center, Nashville, Tennessee, USA
3. ³The Jackson Laboratory, Bar Harbor, Maine, USA

Correspondence: Dr David E. Ong, Department of Biochemistry, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA. E-mail: david.e.ong@vanderbilt.edu

Received 2 October 2006; Revised 5 December 2006; Accepted 14 December 2006; Published online 15 March 2007.

Abstract

Retinoic acid (RA) is essential for maintenance of most epithelial tissues. One RA biosynthesis pathway consists of cellular retinol-binding protein (Crbp), retinol dehydrogenase (Dhrs9/eRoldh), retinal dehydrogenase 1-3 (Aldh1a1-3), and cellular RA-binding protein 2 (Crabp2). Previously, we localized Aldh1a2 and Aldh1a3 to both epithelial and mesenchymal cells within the hair follicle throughout the hair cycle. This study expands that observation by examining the complete pathway of RA biosynthesis and signaling via RA receptors , , and by immunohistochemistry in C57BL/6J mice wax-stripped to initiate and synchronize the cycle. This pathway of RA biosynthesis and signaling localized to the majority of layers of the hair follicle, sebaceous gland, and interfollicular epidermis in a hair cycle-dependent manner, suggesting that RA biosynthesis within the hair follicle is regulated in both a spatial and temporal manner. This localization pattern also revealed insights into epithelial–mesenchymal interactions and differentiation state differences within the RA biosynthesis and signaling pathway, as well as novel observations on nuclear versus cytoplasmic localization of Crabp2 and RA receptors. This complex pattern of RA biosynthesis and signaling identified by immunolocalization suggests that endogenous RA regulates specific aspects of hair follicle growth, differentiation, and cycling.