Abstract
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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Calcitonin Gene-Related Peptide / metabolism
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Cell Count / methods
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Ciliary Neurotrophic Factor / metabolism
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Core Binding Factor Alpha 2 Subunit / genetics
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Core Binding Factor Alpha 2 Subunit / physiology*
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Core Binding Factor Alpha 3 Subunit / genetics
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Core Binding Factor Alpha 3 Subunit / physiology*
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Embryo, Mammalian
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Ganglia, Spinal / cytology*
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Gene Expression Regulation, Developmental / physiology*
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Green Fluorescent Proteins / metabolism
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Immunohistochemistry / methods
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LIM-Homeodomain Proteins
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Mice
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Mice, Transgenic
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Models, Biological
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Neurons, Afferent / classification
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Neurons, Afferent / cytology
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Neurons, Afferent / metabolism*
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Receptor, trkB / metabolism
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Receptor, trkC / genetics
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Signal Transduction / genetics
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Signal Transduction / physiology*
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Substance P / metabolism
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Transcription Factors / metabolism
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tau Proteins / genetics
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Ciliary Neurotrophic Factor
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Core Binding Factor Alpha 2 Subunit
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Core Binding Factor Alpha 3 Subunit
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Homeodomain Proteins
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LIM-Homeodomain Proteins
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Nerve Tissue Proteins
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Runx1 protein, mouse
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Runx3 protein, mouse
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Transcription Factors
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insulin gene enhancer binding protein Isl-1
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tau Proteins
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Hb9 protein, mouse
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Green Fluorescent Proteins
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Neurog1 protein, mouse
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Substance P
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axokine
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Receptor, trkB
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Receptor, trkC
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Calcitonin Gene-Related Peptide