Transcriptional control of motor pool formation and motor circuit connectivity by the LIM-HD protein Isl2
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Abstract
The fidelity of motor control requires the precise positional arrangement of motor pools and the establishment of synaptic connections between these pools. In the developing spinal cord, motor nerves project to specific target muscles and receive proprioceptive input from the muscles via the sensorimotor circuit. LIM-homeodomain transcription factors are known to successively restrict specific motor neuronal fates during neural development; however, it remains unclear to what extent they contribute to limb-based motor pools and locomotor circuits. Here, we showed in mice that deletion of Isl2 resulted in scattered motor pools, primarily in the median motor column and lateral LMC (LMCl) populations, and lacked Pea3 expression in the hindlimb motor pools, accompanied by reduced terminal axon branching and disorganized neuromuscular junctions. Transcriptomic analysis of Isl2 - deficient spinal cords revealed that a variety of genes involved in motor neuron differentiation, axon development, and synapse organization were downregulated in hindlimb motor pools. Moreover, the loss of Isl2 impaired sensorimotor connectivity and hindlimb locomotion. Together, our studies indicate that Isl2 plays a critical role in organizing motor pool position and sensorimotor circuits in hindlimb motor pools.Keywords
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- Published version: eLife, 12.
This publication has 78 references indexed in Scilit:
- Genetics of amyotrophic lateral sclerosis: an updateMolecular Neurodegeneration, 2013
- The LIM-Homeodomain Protein Islet Dictates Motor Neuron Electrical Properties by Regulating K+ Channel ExpressionNeuron, 2012
- Structural Basis for Partial Redundancy in a Class of Transcription Factors, the LIM Homeodomain Proteins, in Neural Cell Type SpecificationJournal of Biological Chemistry, 2011
- Patterns of Spinal Sensory-Motor Connectivity Prescribed by a Dorsoventral Positional TemplateCell, 2011
- Impaired Locomotor Learning and Altered Cerebellar Synaptic Plasticity in pep-19/pcp4-Null MiceMolecular and Cellular Biology, 2011
- Isl1 Is required for multiple aspects of motor neuron developmentMolecular and Cellular Neuroscience, 2011
- Early Functional Impairment of Sensory-Motor Connectivity in a Mouse Model of Spinal Muscular AtrophyNeuron, 2011
- Coordinated Actions of the Forkhead Protein Foxp1 and Hox Proteins in the Columnar Organization of Spinal Motor NeuronsNeuron, 2008
- A Regulatory Network to Segregate the Identity of Neuronal SubtypesDevelopmental Cell, 2008
- Early Motor Neuron Pool Identity and Muscle Nerve Trajectory Defined by Postmitotic Restrictions in Nkx6.1 ActivityNeuron, 2008