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Muscle-selective RUNX3 dependence of sensorimotor circuit development.

Yiqiao Wang1, Haohao Wu1, Pavel Zelenin1

  • 1Department of Neuroscience, Karolinska Institutet, Stockholm 17177, Sweden.

Development (Cambridge, England)
|October 3, 2019
PubMed
Summary

RUNX3 maintains proprioceptive sensory neuron identity and sensorimotor connections. Muscle signals regulate RUNX3, refining specialized neural circuits for motor control.

Keywords:
Dorsal root gangliaNeuronal specificationNeurotrophinsSensorimotor circuitSensory system

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Genetics

Background:

  • Proprioceptive sensory neurons (PSNs) are crucial for motor control, relaying muscle sensory information to the spinal cord.
  • The molecular mechanisms governing the development and maintenance of PSN subtypes and their connections are not fully understood.
  • The transcription factor RUNX3 is known to be vital for early PSN differentiation.

Purpose of the Study:

  • To investigate the role of RUNX3 in later stages of PSN specification and sensorimotor circuit formation.
  • To determine if RUNX3 is required for maintaining PSN identity after peripheral innervation.
  • To explore how RUNX3 influences the selectivity of sensorimotor connections.

Main Methods:

  • Conditional inactivation of the Runx3 gene in PSNs after peripheral innervation.
  • Analysis of PSN cell identity and survival.
  • Assessment of sensorimotor connections at the limb level.
  • Investigation of factors regulating RUNX3 expression in PSNs.

Main Results:

  • Conditional Runx3 inactivation maintains PSN identity in a subgroup of neurons without causing cell death.
  • RUNX3 is essential for sensorimotor connections between PSNs and motor neurons, with variable sensitivity across different muscles.
  • Muscle-derived signals, including neurotrophin 3, are necessary for maintaining RUNX3 expression in PSNs.

Conclusions:

  • RUNX3 acts as a transcriptional regulator essential for specifying generic PSN identity post-neurogenesis.
  • Target muscle-derived signals regulate RUNX3 expression, contributing to the specialized aspects of sensorimotor connection selectivity.
  • This study reveals a mechanism where RUNX3's role evolves from initial specification to fine-tuning neural circuit specialization based on muscle feedback.