Role of the ABC transporter Mdr49 in Hedgehog signaling and germ cell migration. Author Girish Deshpande, Diane Manry, Nicholas Jourjine, Vladic Mogila, Henny Mozes, Tzofia Bialistoky, Offer Gerlitz, Paul Schedl Publication Year 2016 Type Journal Article Abstract Coalescence of the embryonic gonad in Drosophila melanogaster requires directed migration of primordial germ cells (PGCs) towards somatic gonadal precursor cells (SGPs). It was recently proposed that the ATP-binding cassette (ABC) transporter Mdr49 functions in the embryonic mesoderm to facilitate the transmission of the PGC attractant from the SGPs; however, the precise molecular identity of the Mdr49-dependent guidance signal remained elusive. Employing the loss- and gain-of-function strategies, we show that Mdr49 is a component of the Hedgehog (hh) pathway and it potentiates the signaling activity. This function is direct because in Mdr49 mutant embryos the Hh ligand is inappropriately sequestered in the hh-expressing cells. Our data also suggest that the role of Mdr49 is to provide cholesterol for the correct processing of the Hh precursor protein. Supporting this conclusion, PGC migration defects in Mdr49 embryos are substantially ameliorated by a cholesterol-rich diet. Keywords Animals, Drosophila Proteins, Signal Transduction, Mutation, Ligands, Epistasis, Genetic, Drosophila melanogaster, Wings, Animal, Gene Expression Regulation, Developmental, Embryo, Nonmammalian, Zygote, Cell Movement, Epidermis, Germ Cells, Gene Duplication, Alleles, Feeding Behavior, Hedgehog Proteins, Cholesterol, Epidermal Cells, ATP Binding Cassette Transporter, Subfamily B, Homozygote Journal Development Volume 143 Issue 12 Pages 2111-20 Date Published 2016 Jun 15 ISSN Number 1477-9129 DOI 10.1242/dev.133587 Alternate Journal Development PMCID PMC4920174 PMID 27122170 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML