A role for Runx transcription factor signaling in dorsal root ganglion sensory neuron diversification.
Subpopulations of sensory neurons in the dorsal root ganglion (DRG) can be characterized on the basis of sensory modalities that convey distinct peripheral stimuli, but the molecular mechanisms that underlie sensory neuronal diversification remain unclear. Here, we have used genetic manipulations in the mouse embryo to examine how Runx transcription factor signaling controls the acquisition of distinct DRG neuronal subtype identities. Runx3 acts to diversify an Ngn1-independent neuronal cohort by promoting the differentiation of proprioceptive sensory neurons through erosion of TrkB expression in prospective TrkC+ sensory neurons. In contrast, Runx1 controls neuronal diversification within Ngn1-dependent TrkA+ neurons by repression of neuropeptide CGRP expression and controlling the fine pattern of laminar termination in the dorsal spinal cord. Together, our findings suggest that Runx transcription factor signaling plays a key role in sensory neuron diversification.
Kramer
Ina
I
Biozentrum, Department of Cell Biology, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
Sigrist
Markus
M
de Nooij
Joriene C
JC
Taniuchi
Ichiro
I
Jessell
Thomas M
TM
Arber
Silvia
S
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000502:physiology*; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009475:Neurons, Afferent / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism; D020812:Receptor, trkC / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013373:Substance P / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D015740:Calcitonin Gene-Related Peptide; D020934:Ciliary Neurotrophic Factor; D050676:Core Binding Factor Alpha 2 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D020813:Receptor, trkB; D020812:Receptor, trkC; D013373:Substance P; D014157:Transcription Factors; D016875:tau Proteins; C493726:Runx1 protein, mouse; C493730:Runx3 protein, mouse; C063843:insulin gene enhancer binding protein Isl-1; C084059:Hb9 protein, mouse; C486336:Neurog1 protein, mouse; C118937:axokine