Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Transcriptional Reorganization of Drosophila Motor Neurons and Their Muscular Junctions toward a Neuroendocrine Phenotype by the bHLH Protein Dimmed
Stockholm University, Faculty of Science, Department of Zoology.
Stockholm University, Faculty of Science, Department of Zoology.
Stockholm University, Faculty of Science, Department of Zoology.
Number of Authors: 32017 (English)In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 10, article id 260Article in journal (Refereed) Published
Abstract [en]

Neuroendocrine cells store and secrete bulk amounts of neuropeptides, and display morphological and molecular characteristics distinct from neurons signaling with classical neurotransmitters. In Drosophila the transcription factor Dimmed (Dimm), is a prime organizer of neuroendocrine capacity in a majority of the peptidergic neurons. These neurons display large cell bodies and extensive axon terminations that commonly do not form regular synapses. We ask which molecular compartments of a neuron are affected by Dimm to generate these morphological features. Thus, we ectopically expressed Dimm in glutamatergic, Dimm-negative, motor neurons and analyzed their characteristics in the central nervous system and the neuromuscular junction. Ectopic Dimm results in motor neurons with enlarged cell bodies, diminished dendrites, larger axon terminations and boutons, as well as reduced expression of synaptic proteins both pre and post-synaptically. Furthermore, the neurons display diminished vesicular glutamate transporter, and signaling components known to sustain interactions between the developing axon termination and muscle, such as wingless and frizzled are down regulated. Ectopic co-expression of Dimm and the insulin receptor augments most of the above effects on the motor neurons. In summary, ectopic Dimm expression alters the glutamatergic motor neuron phenotype toward a neuroendocrine one, both pre- and post-synaptically. Thus, Dimm is a key organizer of both secretory capacity and morphological features characteristic of neuroendocrine cells, and this transcription factor affects also post- synaptic proteins.

Place, publisher, year, edition, pages
2017. Vol. 10, article id 260
Keywords [en]
transcription factor, neuromuscular junction, synapses, glutamate signaling, neuroendocrine cell
National Category
Biological Sciences
Research subject
Functional Zoomorphology
Identifiers
URN: urn:nbn:se:su:diva-147087DOI: 10.3389/fnmol.2017.00260ISI: 000407622800001OAI: oai:DiVA.org:su-147087DiVA, id: diva2:1149444
Available from: 2017-10-16 Created: 2017-10-16 Last updated: 2018-09-13Bibliographically approved
In thesis
1. Morphological and functional effects of insulin signaling and the bHLH transcription factor Dimmed on different neuron types in Drosophila
Open this publication in new window or tab >>Morphological and functional effects of insulin signaling and the bHLH transcription factor Dimmed on different neuron types in Drosophila
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In Drosophila, the insulin signaling pathway is at the interface between dietary conditions and control of growth and development, reproduction, stress responses and life span. Eight insulin like peptides (Dilp1-8), an insulin tyrosine kinase receptor (dInR) and its downstream components, as well as a relaxin-like receptor type (Lgr3) form the core of this signaling. Here we showed that the dInR mediates post-mitotic cell growth specifically in about 300 peptidergic neurons expressing the basic helix loop helix (bHLH) transcription factor Dimmed (Paper I).  Overexpression of dInR in Dimm positive neurons leads to increased size of cell body, Golgi apparatus and nucleus, whereas dInR knockdown causes an opposite effect. Manipulation of downstream components of insulin signaling induces similar changes in Dimm positive neurons. This mechanism is nutrient dependent. In Paper II, we further investigate the relation between Dimmed and dInR for regulation of cell growth. Coexpressing Dimm and dInR in a range of Dimm negative neurons results in increased cell size in both larval and adult stages. We provide further evidence that dInR regulates cell growth in a Dimm dependent manner and that DILP6 from glia cells is involved in this regulation. In addition, we find that Dimm alone is capable of triggering cell growth in certain neuron types at different developmental stages. Furthermore, ectopic Dimm alone can block apoptosis.  Dimm is a known master regulator of peptidergic cell fate. In paper III we find that ectopic expression of Dimm in Dimm negative motor neurons results in transformation the neurons towards a neuroendocrine phenotype. They acquire enlarged axon terminations and boutons, lose both pre- and postsynaptic markers, and display diminished levels of wingless and its receptor dFrizzled. Furthermore they show increased expression of several Dimm targets. Finally, combined ectopic Dimm and dInR expression gives rise to stronger phenotypes. In paper IV we studied another DILP possibly involved in growth regulation, the under-investigated DILP1. We generated Dilp1-Gal4 lines and anti DILP1 antibodies and found that DILP1 is transiently expressed in brain insulin producing cells (IPCs) from pupal stages to newly hatched adult flies. Diapausing virgin female flies display a high expression level of dilp1/DILP1 over at least 9 weeks of adult life. DILP1 expression is also correlated with the persistence of larval/pupal fat body and its expression is regulated by other DILPs and short neuropeptide F (sNPF). Flies mutant in dilp1 display increased food intake, but decreased stress resistance and life span. We found no obvious role of DILP1 in growth regulation.

Place, publisher, year, edition, pages
Stockholm University, 2016. p. 41
Keywords
insulin signaling, Dimm, neuropeptide, insulin receptor, insulin-like peptide, drosophila
National Category
Natural Sciences Biological Sciences
Research subject
Functional Zoomorphology
Identifiers
urn:nbn:se:su:diva-125941 (URN)978-91-7649-283-3 (ISBN)
Public defence
2016-02-26, Ahlmannsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Manuscript. Paper 3: Manuscript. Paper 4: Manuscript.

Available from: 2016-02-03 Created: 2016-01-20 Last updated: 2018-09-13Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full text

Search in DiVA

By author/editor
Luo, JiangnanLiu, YitingNässel, Dick R.
By organisation
Department of Zoology
In the same journal
Frontiers in Molecular Neuroscience
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 69 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf