@article{203986,
  keywords = {Animals, Neurons, signal transduction, Membrane Proteins, Gene Expression Regulation, Developmental, Cell Movement, Heterozygote, Drosophila melanogaster, Drosophila Proteins, Germ Cells, Niemann-Pick C1 Protein},
  author = {Tzofia Bialistoky and Diane Manry and Peyton Smith and Christopher Ng and Yunah Kim and Sol Zamir and Victoria Moyal and Rachel Kalifa and Paul Schedl and Offer Gerlitz and Girish Deshpande},
  title = {Functional analysis of Niemann-Pick disease type C family protein, NPC1a, in },
  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. },
  year = {2019},
  journal = {Development},
  volume = {146},
  month = {05/2019},
  issn = {1477-9129},
  doi = {10.1242/dev.168427},
  language = {eng},
}