SLC7 family transporters control the establishment of left-right asymmetry during organogenesis in medaka by activating mTOR signaling

Yoichi Asaoka, Yoko Nagai, Misako Namae, Makoto Furutani-Seiki, Hiroshi Nishina

Research output: Contribution to journalArticlepeer-review

6 Citations (SciVal)

Abstract

The precise government of the left-right (LR) specification of an organ is an essential aspect of its morphogenesis. Multiple signaling cascades have been implicated in the establishment of vertebrate LR asymmetry. Recently, mTOR signaling was found to critically regulate the development of LR asymmetry in zebrafish. However, the upstream factor(s) that activate mTOR signaling in the context of LR specification are as yet unknown. In this study, we identify the SLC7 amino acid transporters Slc7a7 and Slc7a8 as novel regulators of LR asymmetry development in the small fish medaka. Knockdown of Slc7a7 and/or Slc7a8 in medaka embryos disrupted LR organ asymmetries. Depletion of Slc7a7 hindered left-sided expression of the southpaw (spaw) gene, which is responsible for LR axis determination. Work at the cellular level revealed that Slc7a7 coordinates ciliogenesis in the epithelium of Kupffer's vesicle and thereby the generation of the nodal fluid flow required for LR asymmetry. Interestingly, knockdown of Slc7a7 depressed mTOR signaling activity in medaka embryos. Treatment with rapamycin, an inhibitor of mTOR signaling, together with Slc7a7 knockdown synergistically perturbed spaw expression, indicating an interaction between Slc7a7 and mTOR signaling affecting gene expression required for LR specification. Taken together, our results demonstrate that Slc7a7 governs the regulation of LR asymmetry development via the activation of mTOR signaling.

Original languageEnglish
Pages (from-to)146-153
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume474
Issue number1
DOIs
Publication statusPublished - 20 May 2016

Keywords

  • Ciliogenesis
  • Left-right asymmetry
  • Medaka
  • mTOR signaling
  • Nodal flow
  • SLC7 transporter

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Molecular Biology

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