title: The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ditsa
authors.initials: D
authors.lastname: Levanon
authors.forename: David
authors.initials: D
authors.lastname: Bettoun
authors.forename: Catherine
authors.initials: C
authors.lastname: Harris-Cerruti
authors.forename: Eilon
authors.initials: E
authors.lastname: Woolf
authors.forename: Varda
authors.initials: V
authors.lastname: Negreanu
authors.forename: Raya
authors.initials: R
authors.lastname: Eilam
authors.forename: Yael
authors.initials: Y
authors.lastname: Bernstein
authors.forename: Dalia
authors.initials: D
authors.lastname: Goldenberg
authors.forename: Cuiying
authors.initials: C
authors.lastname: Xiao
authors.forename: Manfred
authors.initials: M
authors.lastname: Fliegauf
authors.forename: Eitan
authors.initials: E
authors.lastname: Kremer
authors.forename: Florian
authors.initials: F
authors.lastname: Otto
authors.forename: Ori
authors.initials: O
authors.lastname: Brenner
authors.forename: Aharon
authors.initials: A
authors.lastname: Lev-Tov
authors.forename: Yoram
authors.initials: Y
authors.lastname: Groner
mesh_terms: D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D001259:Ataxia / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D001369:Axons / Q000648:ultrastructure; D015415:Biomarkers; D016923:Cell Death; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005727:Ganglia, Spinal / Q000737:chemistry / Q000473:pathology*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009046:Motor Neurons / Q000502:physiology; D009470:Muscle Spindles / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009475:Neurons, Afferent / Q000166:cytology*; D010320:Parvalbumins / Q000032:analysis; D011434:Proprioception / Q000235:genetics / Q000502:physiology*; D020812:Receptor, trkC / Q000032:analysis*; D020886:Somatosensory Disorders / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology; D013569:Synapses / Q000473:pathology; D009435:Synaptic Transmission; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000737:chemistry / Q000473:pathology; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D015415:Biomarkers; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; C493730:Runx3 protein, mouse; D014157:Transcription Factors; D020812:Receptor, trkC; D001616:beta-Galactosidase