Functional analysis of niemann-pick disease type C family protein, NPC1a, in Drosophila melanogaster

Tzofia Bialistoky, Diane Manry, Peyton Smith, Christopher Ng, Yunah Kim, Sol Zamir, Victoria Moyal, Rachel Kalifa, Paul Schedl, Offer Gerlitz, Girish Deshpande

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Article numberdev168427
JournalDevelopment (Cambridge)
Issue number10
StatePublished - May 2019

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology


  • Cell migration
  • Drosophila melanogaster
  • Embryogenesis
  • Primordial germ cells


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