Functional analysis of Niemann-Pick disease type C family protein, NPC1a, in . Author Tzofia Bialistoky, Diane Manry, Peyton Smith, Christopher Ng, Yunah Kim, Sol Zamir, Victoria Moyal, Rachel Kalifa, Paul Schedl, Offer Gerlitz, Girish Deshpande Publication Year 2019 Type Journal Article Abstract 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 , 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 results in germ cell migration defects. Similar to , PGC migration defects in the embryos are ameliorated by a cholesterol-rich diet. Consistently, reduction in weakens the ability of ectopic HMG Coenzyme A reductase () to induce germ cell migration defects. Moreover, compromising levels influences Hh signaling adversely during wing development, a process that relies upon long-range Hh signaling. Last, doubly heterozygous embryos () display enhanced germ cell migration defects when compared with single mutants ( or ), supporting cooperative interaction between the two. Keywords Animals, Drosophila Proteins, Signal Transduction, Membrane Proteins, Drosophila melanogaster, Neurons, Gene Expression Regulation, Developmental, Cell Movement, Germ Cells, Heterozygote, Niemann-Pick C1 Protein Journal Development Volume 146 Issue 10 Date Published 2019 May 15 ISSN Number 1477-9129 DOI 10.1242/dev.168427 Alternate Journal Development PMCID PMC6550021 PMID 31092503 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML