Positional variation in the molecular regulation of mammary gland development

Abstract

Our lab aims to unravel the molecular mechanisms of early mammogenesis, using the five pairs of mammary glands in mouse embryos as a model. We found that loss of Gli3 results in induction of only mammary rudiment pairs #1, #2 and #4, but not #3 and #5. Moreover, the #2 and #4 pairs each have distinct morphogenetic defects, while pair #1 is morphologically normal. Our in vivo approach to rescue all defects by activating a pathway downstream of Gli3 resulted in induction of pair #3 only, but not of pair #5, nor did it restore morphogenesis of pairs #2 and #4. Analysis of the latter two pairs is ongoing. We conclude that all five pairs of mammary rudiments in mice differ in their molecular regulation of induction and early morphogenesis, despite their identical functional outcome. This contrasts with other multiples of the same structures, e.g. somites, limbs or hair follicles, which are generally thought to share the same inductive signals, while unique specification signals establish their anatomical and functional differences such as those between fore‐ and hind limbs. The variation in molecular inductive mechanisms of mammary glands may explain the differences in numbers and positions of mammary glands among mammalian species. It also increases the chances of survival of the species when a gene function is altered.Funding provided by CBCRP:10FB‐0116 and A*STAR.Grant Funding Source: A*STAR