Drosophila larval to pupal switch under nutrient stress requires IP3R/Ca2+ signalling in glutamatergic interneurons

  1. Siddharth Jayakumar
  2. Shlesha Richhariya
  3. O Venkateswara Reddy
  4. Michael J Texada
  5. Gaiti Hasan  Is a corresponding author
  1. Tata Institute of Fundamental Research, India
  2. Janelia Research Campus, Howard Hughes Medical Institute, United States

Abstract

Neuronal circuits are known to integrate nutritional information, but the identity of the circuit components is not completely understood. Amino acids are a class of nutrients that are vital for the growth and function of an organism. Here, we report a neuronal circuit that allows Drosophila larvae to overcome amino acid deprivation and pupariate. We find that nutrient stress is sensed by the class IV multidendritic cholinergic neurons. Through live calcium imaging experiments, we show that these cholinergic stimuli are conveyed to glutamatergic neurons in the ventral ganglion through mAChR. We further show that IP3R-dependent calcium transients in the glutamatergic neurons convey this signal to downstream medial neurosecretory cells (mNSCs). The circuit ultimately converges at the ring gland and regulates expression of ecdysteroid biosynthetic genes. Activity in this circuit is thus likely to be an adaptation that provides a layer of regulation to help surpass nutritional stress during development.

Article and author information

Author details

  1. Siddharth Jayakumar

    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  2. Shlesha Richhariya

    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  3. O Venkateswara Reddy

    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    Competing interests
    The authors declare that no competing interests exist.
  4. Michael J Texada

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2479-1241
  5. Gaiti Hasan

    National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
    For correspondence
    gaiti@ncbs.res.in
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7194-383X

Funding

National Centre for Biological Sciences (Core funding)

  • Gaiti Hasan

Council of Scientific and Industrial Research (Graduate fellowship)

  • Siddharth Jayakumar

National Centre for Biological Sciences (Graduate fellowship)

  • Shlesha Richhariya

Howard Hughes Medical Institute

  • Gaiti Hasan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2016, Jayakumar et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 4,303
    views
  • 697
    downloads
  • 27
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Siddharth Jayakumar
  2. Shlesha Richhariya
  3. O Venkateswara Reddy
  4. Michael J Texada
  5. Gaiti Hasan
(2016)
Drosophila larval to pupal switch under nutrient stress requires IP3R/Ca2+ signalling in glutamatergic interneurons
eLife 5:e17495.
https://doi.org/10.7554/eLife.17495

Share this article

https://doi.org/10.7554/eLife.17495

Further reading

    1. Neuroscience
    Giordano de Guglielmo, Lieselot Carrette ... Olivier George
    Research Article

    Addiction is commonly characterized by escalation of drug intake, compulsive drug seeking, and continued use despite harmful consequences. However, the factors contributing to the transition from moderate drug use to these problematic patterns remain unclear, particularly regarding the role of sex. Many preclinical studies have been limited by small sample sizes, low genetic diversity, and restricted drug access, making it challenging to model significant levels of intoxication or dependence and translate findings to humans. To address these limitations, we characterized addiction-like behaviors in a large sample of >500 outbred heterogeneous stock (HS) rats using an extended cocaine self-administration paradigm (6 hr/daily). We analyzed individual differences in escalation of intake, progressive ratio (PR) responding, continued use despite adverse consequences (contingent foot shocks), and irritability-like behavior during withdrawal. Principal component analysis showed that escalation of intake, progressive ratio responding, and continued use despite adverse consequences loaded onto a single factor that was distinct from irritability-like behaviors. Categorizing rats into resilient, mild, moderate, and severe addiction-like phenotypes showed that females exhibited higher addiction-like behaviors, with a lower proportion of resilient individuals compared to males. These findings suggest that, in genetically diverse rats with extended drug access, escalation of intake, continued use despite adverse consequences, and PR responding are highly correlated measures of a shared underlying construct. Furthermore, our results highlight sex differences in resilience to addiction-like behaviors.

    1. Neuroscience
    Tingting Li, Wenwen Shi ... Yong Q Zhang
    Research Article

    Traumatic brain injury (TBI) caused by external mechanical forces is a major health burden worldwide, but the underlying mechanism in glia remains largely unclear. We report herein that Drosophila adults exhibit a defective blood–brain barrier, elevated innate immune responses, and astrocyte swelling upon consecutive strikes with a high-impact trauma device. RNA sequencing (RNA-seq) analysis of these astrocytes revealed upregulated expression of genes encoding PDGF and VEGF receptor-related (Pvr, a receptor tyrosine kinase), adaptor protein complex 1 (AP-1, a transcription factor complex of the c-Jun N-terminal kinase pathway) composed of Jun-related antigen (Jra) and kayak (kay), and matrix metalloproteinase 1 (Mmp1) following TBI. Interestingly, Pvr is both required and sufficient for AP-1 and Mmp1 upregulation, while knockdown of AP-1 expression in the background of Pvr overexpression in astrocytes rescued Mmp1 upregulation upon TBI, indicating that Pvr acts as the upstream receptor for the downstream AP-1–Mmp1 transduction. Moreover, dynamin-associated endocytosis was found to be an important regulatory step in downregulating Pvr signaling. Our results identify a new Pvr–AP-1–Mmp1 signaling pathway in astrocytes in response to TBI, providing potential targets for developing new therapeutic strategies for TBI.