Abstract A121: Retinoic acid signaling and initiation of mammary gland development

Abstract

Abstract Mammary glands are skin appendages whose development is initiated through continuous cell-cell interactions between ectoderm and adjacent mesenchyme. Considerable progress has been made in uncovering the molecular basis of these interactions in mammary gland formation in mouse embryos, including the network of initiating signals comprising Fgfs and Wnts, Bmps involved in gland positioning and transcription factors, Tbx3 and Lef1, essential for mammary gland development. Here we provide evidence that retinoic acid signaling may also be involved. Raldh2 is expressed in E10-E10.5 mouse embryos in ventral hypaxial extensions of somites adjacent to the flank region where mammary buds 2, 3 and 4 develop. This pattern of expression overlaps with that of Fgf10, known to be required for mammary gland formation. Manipulation of retinoic acid levels in organ cultures of E10.5 mouse embryo flank by adding either retinoic acid or citral, a retinoic acid synthesis inhibitor, resulted in changes in expression of genes involved in retinoic acid homeostasis and also showed that retinoic acid signaling is required for Tbx3 expression while high levels of retinoic acid signaling inhibit Bmp4 expression and repress Wnt signaling. The results of experiments using RNAi against Tbx3 and Wnt10b suggest that manipulating RA signaling in the mammary gland forming regions. Furthermore, RA affects expression of genes involved in mammary gland initiation. We produce a molecular model for mammary gland initiation incorporating retinoic acid signaling. Citation Format: Kyoung-Won Cho, Woo-Kyung Moon. Retinoic acid signaling and initiation of mammary gland development. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Breast Cancer Research: Genetics, Biology, and Clinical Applications; Oct 3-6, 2013; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2013;11(10 Suppl):Abstract nr A121.