Evidence map›Paper›PMID 23222439›Full record

ArticleDevelopment (Cambridge, England)2013

Sim1a and Arnt2 contribute to hypothalamo-spinal axon guidance by regulating Robo2 activity via a Robo3-dependent mechanism.

Jörn Schweitzer, Heiko Löhr, Joshua L Bonkowsky, Katrin Hübscher, Wolfgang Driever

Open access · bronzeAbstract read
In one paragraph

Article in Development (Cambridge, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.6field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 30 citations in OpenAlex.

  1. Transcriptional profiling of extraocular motor neurons revealsbioRxiv : the preprint server for biology · 2026
    Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. The Temporal Neurogenesis Patterning of Spinal p3-V3 Interneurons into Divergent Subpopulation Assemblies.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
  7. Review
  8. Article
  9. Netrin1-DCC-Mediated Attraction Guides Post-Crossing Commissural Axons in the Hindbrain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015
    Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Transcriptional regulation of guidance at the midline and in motor circuits.Cellular and molecular life sciences : CMLS · 2014
    Review
  15. Article
  16. Patterning, specification, and differentiation in the developing hypothalamus.Wiley interdisciplinary reviews. Developmental biology
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Jörn SchweitzerDevelopmental Biology, Institute Biology 1, Faculty of Biology, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg, Germany. joern.schweitzer@biologie.uni-freiburg.de
Heiko Löhr
Joshua L Bonkowsky
Katrin Hübscher
Wolfgang Driever
University of Freiburg · DE

Funding

Trans-Cellular Activation of Transcription to Analyze Dopaminergic Axon ReorganizDP2MH100008 · NIMH · UNIVERSITY OF UTAH · PI BONKOWSKY, JOSH LEITCH · 2012 to 2012
$2.2M
Characterization and Genetic Analysis of Basal Ganglia Axon PathfindingK08DA024753 · NIDA · UNIVERSITY OF UTAH · PI BONKOWSKY, JOSH LEITCH · 2008 to 2013
$931k
NIDA NIH HHS K08 DA024753NIMH NIH HHS DP2 MH100008
6 · The paper itself

Abstract

Precise spatiotemporal control of axon guidance factor expression is a prerequisite for formation of functional neuronal connections. Although Netrin/Dcc- and Robo/Slit-mediated attractive and repulsive guidance of commissural axons have been extensively studied, little is known about mechanisms controlling mediolateral positioning of longitudinal axons in vertebrates. Here, we use a genetic approach in zebrafish embryos to study pathfinding mechanisms of dopaminergic and neuroendocrine longitudinal axons projecting from the hypothalamus into hindbrain and spinal cord. The transcription factors Sim1a and Arnt2 contribute to differentiation of a defined population of dopaminergic and neuroendocrine neurons. We show that both factors also control aspects of axon guidance: Sim1a or Arnt2 depletion results in displacement of hypothalamo-spinal longitudinal axons towards the midline. This phenotype is suppressed in robo3 guidance receptor mutant embryos. In the absence of Sim1a and Arnt2, expression of the robo3 splice isoform robo3a.1 is increased in the hypothalamus, indicating negative control of robo3a.1 transcription by these factors. We further provide evidence that increased Robo3a.1 levels interfere with Robo2-mediated repulsive axon guidance. Finally, we show that the N-terminal domain unique to Robo3a.1 mediates the block of Robo2 repulsive activity. Therefore, Sim1a and Arnt2 contribute to control of lateral positioning of longitudinal hypothalamic-spinal axons by negative regulation of robo3a.1 expression, which in turn attenuates the repulsive activity of Robo2.

Indexed as

AnimalsAryl Hydrocarbon Receptor Nuclear TranslocatorBasic Helix-Loop-Helix ProteinsHypothalamusNerve Tissue ProteinsReceptors, ImmunologicRepressor ProteinsRNA SplicingRoundabout ProteinsSpinal CordZebrafishZebrafish Proteinsarnt2 protein, zebrafishAryl Hydrocarbon Receptor Nuclear TranslocatorBasic Helix-Loop-Helix ProteinsNerve Tissue ProteinsReceptors, ImmunologicRepressor Proteinsrobo2 protein, zebrafishrobo3 protein, zebrafishRoundabout ProteinsSim1a protein, zebrafishZebrafish Proteins

Identifiers

PMID23222439
PMCPMC4497291
OpenAlexW2090036110

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.