Adipocyte derived paracrine mediators of mammary ductal morphogenesis controlled by retinoic acid receptors

►Generation of a new transgenic model expressing a dominant negative RARα (G303E) under the control of the adipocyte-specific promoter (aP2). ►Strong impairment of pubertal and mature mammary ductal tree development associated with a pronounced decreased proliferation. ►Adipocyte-RARs contribute to generation of secreted proliferative and pro-migratory factors. ►Pleiotrophin (PTN) was identified as the paracrine effectors of epithelial cell migration and adipocyte-PTHR, another atRA responsive gene, was found to be an up-stream regulator of PTN. ►The results support the existence of a novel paracrine loop controlled by adipocyte-RAR that regulates the mammary ductal tree morphogenesis.