Functional Analysis of ABC Transporter Mdr49 and Cholesterol Metabolism during germ cell Migration in Drosophila Melanogaster

Abstract

In Drosophila, the primitive embryonic gonad is comprised of two cell types with distinct origins: somatic gonadal precursor cells (SGPs) and primordial germ cells (PGCs). During the course of embryogenesis, PGCs formed at the posterior of the embryo undertake a complex migratory journey across different cell layers in order to travel towards and associate with the SGPs in the gonadal mesoderm. It is generally accepted that attractive and repulsive cues are necessary to guide germ cells during migration. The signaling ligand Hh and a biosynthetic enzyme, Hmgcr, are two components that contribute to the chemoattractive influence that guides migrating germ cells towards SGPs. In this study, we explore the involvement of an ABC transporter, multi-drug-resistant-49 (mdr49), in the germ cell migration pathway. Mutations in mdr49 confer germ cell migration defects, and also dominantly suppress the mutant phenotype caused by a hh gain-of-function allele in the adult fly. Conversely, loss-of-function of mdr49 exacerbates germ cell migration defects caused by misexpression of hmgcr in the central nervous system (CNS). We also present findings concerning a novel component of the germ cell migration pathway, a cholesterol transporter called Niemann-Pick C1a (npc1a). Through a series of cholesterol-feeding experiments, we provide evidence for the involvement of mdr49, npc1a, and cholesterol itself in the process of modifying and exporting a germ cell attractant.