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The Runx1/AML1 transcription factor selectively regulates development and survival of TrkA nociceptive sensory neurons

Nature Neuroscience volume 9, pages 180–187 (2006)Cite this article

Abstract

Neural crest cells (NCCs) can adopt different neuronal fates. In NCCs, neurogenin-2 promotes sensory specification but does not specify different subclasses of sensory neurons. Understanding the gene cascades that direct Trk gene activation may reveal mechanisms generating sensory diversity, because different Trks are expressed in different sensory neuron subpopulations. Here we show in chick and mouse that the Runt transcription factor Runx1 promotes axonal growth, is selectively expressed in neural crest–derived TrkA+ sensory neurons and mediates TrkA transactivation in migratory NCCs. Inhibition of Runt activity depletes TrkA expression and leads to neuronal death. Moreover, Runx1 overexpression is incompatible with multipotency in the migratory neural crest but does not induce expression of pan-neuronal genes. Instead, Runx1-induced neuronal differentiation depends on an existing neurogenin2 proneural gene program. Our data show that Runx1 directs, in a context-dependent manner, key aspects of the establishment of the TrkA+ nociceptive subclass of neurons.

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Figure 1: RuntB is expressed in the TrkA+ subpopulation of neural crest–derived trunk and cranial sensory neurons.
Figure 2: Runx1b promotes survival and axonal growth of Ngn2-fated bNCSCs.
Figure 3: Blocking Runt activity is incompatible with establishment of neural crest–derived sensory neurons.
Figure 4: Runx1d-induced apoptosis is preceded by a loss of Trk expression.
Figure 5: Runx1b-expressing cells lose Sox10 expression.
Figure 6: Runx1 selectively controls TrkA expression.

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Acknowledgements

We thank C. Tello for technical assistance and A. Käller for secretarial assistance. This work was supported by the Swedish Medical Research Council, the Swedish Foundation for Strategic Research (grant from the Center of Excellence in Developmental Biology), the Hedlunds Foundation, AstraZeneca Mölndal and the US Public Health Service (grant NS 16033).

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Author notes

  1. Frédéric Marmigère and Andreas Montelius: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular Neurobiology, Karolinska Institute, MBB, Scheeles väg 1, Stockholm, Sweden

    Frédéric Marmigère, Andreas Montelius & Patrik Ernfors

  2. Institute of Biochemistry, Friedrich-Alexander-University, Erlangen-Nurnberg, Erlangen, 91054, Germany

    Michael Wegner

  3. Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, 76100, Israel

    Yoram Groner

  4. Howard Hughes Medical Institute and Department of Physiology, University of California San Francisco, San Francisco, 94143, California, USA

    Louis F Reichardt

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Correspondence to Patrik Ernfors.

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Supplementary information

Supplementary Fig. 1

RuntB expression in chick cranial sensory ganglia at stage HH29. (PDF 35108 kb)

Supplementary Fig. 2

Characterisation of proneural gene expression in bNCSCs and a cell autonomous function of Runx1 in cell survival. (PDF 383 kb)

Supplementary Fig. 3

Electroporation of DNA constructs into the chick leads to overexpression in cell populations of neural crest origin. (PDF 11292 kb)

Supplementary Fig. 4

Blocking Runt activity is incompatible with neuronal differentiation in the DRG. (PDF 2634 kb)

Supplementary Fig. 5

Identification of a conserved Runt binding site in vertebrate TrkA minimal enhancers and in vitro transactivation of the promoter by Runx1. (PDF 3148 kb)

Supplementary Fig. 6

Genetic interaction between Runx1 and other transcriptional regulators during sensory neuron development. DRG sensory neurons are derived from NCCs. (PDF 545 kb)

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Marmigère, F., Montelius, A., Wegner, M. et al. The Runx1/AML1 transcription factor selectively regulates development and survival of TrkA nociceptive sensory neurons. Nat Neurosci 9, 180–187 (2006). https://doi.org/10.1038/nn1631

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