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Functional analysis of Niemann-Pick disease type C family protein, NPC1a, in Drosophila melanogaster.
Bialistoky, Tzofia; Manry, Diane; Smith, Peyton; Ng, Christopher; Kim, Yunah; Zamir, Sol; Moyal, Victoria; Kalifa, Rachel; Schedl, Paul; Gerlitz, Offer; Deshpande, Girish.
Afiliação
  • Bialistoky T; Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
  • Manry D; Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
  • Smith P; Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
  • Ng C; Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
  • Kim Y; Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
  • Zamir S; Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
  • Moyal V; Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
  • Kalifa R; Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
  • Schedl P; Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.
  • Gerlitz O; Developmental Biology and Cancer Research, The Institute for Medical Research Israel-Canada (IMRIC), The Hebrew University-Hadassah Medical School, Jerusalem, Israel gdeshpan@princeton.edu offerg@ekmd.huji.ac.il.
  • Deshpande G; Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA gdeshpan@princeton.edu offerg@ekmd.huji.ac.il.
Development ; 146(10)2019 05 15.
Article em En | MEDLINE | ID: mdl-31092503
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas de Drosophila / Proteínas de Membrana Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas de Drosophila / Proteínas de Membrana Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article