VANGL2 INFLUENCES PRIMARY CILIA IN THE MURINE MAMMARY GLAND
Oscar Fernandez-Cazares, Prestina Smith, Lindsay Hinck.
University of California, Santa Cruz, Santa Cruz, CA.
The mammary gland (MG), or breast, is a branched epithelial ductal structure that originates at the nipple and grows to fill the mammary fat pad. Each duct is composed of an outer layer of myoepithelial cells (MECs) encircling an inner layer of luminal epithelial cells (LECs). MG growth involves many factors coupled with signaling events including WNT and Hedgehog (Hh) signaling. The planar cell polarity (PCP) pathway, incorporating non-canonical WNT signaling, controls VANGL2 function along with cilia orientation. VANGL2 is required for normal development of branched organs such as the kidney and lung, but its function has not yet been identified in the MG. To investigate, we examined primary cilia in loss-of-function Vangl2lp/lp(LP) mammary outgrowths, comparing them to wild type (WT) by immunostaining with anti-acetylated tubulin to stain cilia structure and anti-gamma tubulin to stain the centrosome. We found that Vangl2lp/lp mammary outgrowth shows more than one cilium per cell in the LEC compartment and fewer cells containing cilia in the MEC compartment, suggesting that VANGL2 regulates cilia numbers. In addition, we observe that Vangl2lp/lp mammary outgrowths have stunted growth and exhibit ductal size differences. Current studies focus on understanding how VANGL2 regulates primary cilia, and if VANGL2 signals through the WNT/PCP pathway or by novel mechanisms. Our studies provide new insight into mammary gland development.