Nature Neuroscience 9, 180 - 187 (2006)
Published online: 22 January 2006; | doi:10.1038/nn1631
The Runx1/AML1 transcription factor selectively regulates development and survival of TrkA nociceptive sensory neuronsFrédéric Marmigère1, 5, Andreas Montelius1, 5, Michael Wegner2, Yoram Groner3, Louis F Reichardt4
& Patrik Ernfors11
Laboratory of Molecular Neurobiology, Karolinska Institute, MBB, Scheeles väg 1, Stockholm, Sweden. 2
Institute of Biochemistry, Friedrich-Alexander-University, Erlangen-Nurnberg, Erlangen 91054, Germany. 3
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel. 4
Howard Hughes Medical Institute and Department of Physiology, University of California San Francisco, San Francisco, California 94143, USA. 5
These authors contributed equally to this work.
Correspondence should be addressed to Patrik Ernfors Patrik.Ernfors@ki.se 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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