RT Journal Article SR Electronic T1 Functional analysis of Niemann-Pick disease type C family protein, NPC1a, in Drosophila melanogaster JF Development JO Development FD The Company of Biologists Limited SP dev168427 DO 10.1242/dev.168427 VO 146 IS 10 A1 Bialistoky, Tzofia A1 Manry, Diane A1 Smith, Peyton A1 Ng, Christopher A1 Kim, Yunah A1 Zamir, Sol A1 Moyal, Victoria A1 Kalifa, Rachel A1 Schedl, Paul A1 Gerlitz, Offer A1 Deshpande, Girish YR 2019 UL http://dev.biologists.org/content/146/10/dev168427.abstract AB During embryonic gonad coalescence, primordial germ cells (PGCs) follow a carefully choreographed migratory route circumscribed by guidance signals towards somatic gonadal precursor cells (SGPs). In Drosophila melanogaster, SGP-derived Hedgehog (Hh), which serves as a guidance cue for the PGCs, is potentiated by mesodermally restricted HMGCoA-reductase (Hmgcr) and the ABC transporter Multi-drug-resistant-49 (Mdr49). Given the importance of cholesterol modification in the processing and long-distance transmission of the Hh ligand, we have analyzed the involvement of the Niemann-Pick disease type C-1a (NPC1a) protein, a cholesterol transporter, in germ cell migration and Hedgehog signaling. We show that mesoderm-specific inactivation of Npc1a results in germ cell migration defects. Similar to Mdr49, PGC migration defects in the Npc1a embryos are ameliorated by a cholesterol-rich diet. Consistently, reduction in Npc1a weakens the ability of ectopic HMG Coenzyme A reductase (Hmgcr) to induce germ cell migration defects. Moreover, compromising Npc1a levels influences Hh signaling adversely during wing development, a process that relies upon long-range Hh signaling. Last, doubly heterozygous embryos (Mdr49/Npc1a) display enhanced germ cell migration defects when compared with single mutants (Npc1a/+ or Mdr49/+), supporting cooperative interaction between the two.