Asynchronous transcription and translation of neurotransmitter-related genes characterize the initial stages of neuronal maturation in Drosophila

PLoS Biol. 2023 May 19;21(5):e3002115. doi: 10.1371/journal.pbio.3002115. eCollection 2023 May.

Abstract

Neuron specification and maturation are essential for proper central nervous system development. However, the precise mechanisms that govern neuronal maturation, essential to shape and maintain neuronal circuitry, remain poorly understood. Here, we analyse early-born secondary neurons in the Drosophila larval brain, revealing that the early maturation of secondary neurons goes through 3 consecutive phases: (1) Immediately after birth, neurons express pan-neuronal markers but do not transcribe terminal differentiation genes; (2) Transcription of terminal differentiation genes, such as neurotransmitter-related genes VGlut, ChAT, or Gad1, starts shortly after neuron birth, but these transcripts are, however, not translated; (3) Translation of neurotransmitter-related genes only begins several hours later in mid-pupa stages in a coordinated manner with animal developmental stage, albeit in an ecdysone-independent manner. These results support a model where temporal regulation of transcription and translation of neurotransmitter-related genes is an important mechanism to coordinate neuron maturation with brain development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila* / metabolism
  • Ecdysone
  • Gene Expression Regulation, Developmental
  • Neurogenesis
  • Neurons / physiology

Substances

  • Drosophila Proteins
  • Ecdysone

Grants and funding

This project has received funding from the European Research Council (ERC; https://erc.europa.eu/) under the European Union’s Horizon 2020 research and innovation programme (H2020-ERC-2017-STG-GA 759853-StemCellHabitat to C.C.F.H.); by Wellcome Trust (https://wellcome.org/grant-funding) and Howard Hughes Medical Institute (https://www.hhmi.org/; HHMI-208581/Z/17/Z-Metabolic Reg SC fate to C.C.F.H.); European Molecular Biology Organization (EMBO) Installation grant (https://www.embo.org/; H2020-EMBO-3311/2017/G2017 to C.C.F.H.); by Fundação para a Ciência e Tecnologia (https://www.fct.pt/; PTDC/BIA-BID/0681/2021; IF/01265/2014/CP1252/CT0004 to C.C.F.H. and PD/BD/114253/2016 to G.S.M.). N.K. was supported by the National Eye Institute (https://www.nei.nih.gov/; K99 EY029356-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.