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Publication : The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons.

First Author  Levanon D Year  2002
Journal  EMBO J Volume  21
Issue  13 Pages  3454-63
PubMed ID  12093746 Mgi Jnum  J:77764
Mgi Id  MGI:2182529 Doi  10.1093/emboj/cdf370
Citation  Levanon D, et al. (2002) The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons. EMBO J 21(13):3454-63
abstractText  The RUNX transcription factors are important regulators of linage-specific gene expression in major developmental pathways. Recently, we demonstrated that Runx3 is highly expressed in developing cranial and dorsal root ganglia (DRGs). Here we report that within the DRGs, Runx3 is specifically expressed in a subset of neurons, the tyrosine kinase receptor C (TrkC) proprioceptive neurons. We show that Runx3-deficient mice develop severe limb ataxia due to disruption of monosynaptic connectivity between intra spinal afferents and motoneurons. We demonstrate that the underlying cause of the defect is a loss of DRG proprioceptive neurons, reflected by a decreased number of TrkC-, parvalbumin- and beta-galactosidase-positive cells. Thus, Runx3 is a neurogenic TrkC neuron-specific transcription factor. In its absence, TrkC neurons in the DRG do not survive long enough to extend their axons toward target cells, resulting in lack of connectivity and ataxia. The data provide new genetic insights into the neurogenesis of DRGs and may help elucidate the molecular mechanisms underlying somatosensory-related ataxia in humans.
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