Abstract:
How CNS circuits sculpt their axonal arbors into spatially and functionally organized domains is not well understood. Segmental specificity of corticospinal connectivity is an exemplar for such regional specificity of many axon projections. Corticospinal neurons (CSN) innervate spinal and brainstem targets with segmental precision, controlling voluntary movement. Multiple molecularly distinct CSN subpopulations innervate the cervical cord for evolutionarily enhanced precision of forelimb movement. Evolutionarily newer CSN(BC-lat) exclusively innervate bulbar-cervical targets, while CSN(medial) are heterogeneous; distinct subpopulations extend axons to either bulbar-cervical or thoraco-lumbar segments. We identify that Lumican controls balance of cervical innervation between CSN(BC-lat) and CSN(medial) axons during development, which is maintained into maturity. Lumican, an extracellular proteoglycan expressed by CSN(BC-lat), non-cell-autonomously suppresses cervical collateralization by multiple CSN(medial) subpopulations. This inter-axonal molecular crosstalk between CSN subpopulations controls murine corticospinal circuitry refinement and forelimb dexterity. Such crosstalk is generalizable beyond the corticospinal system for evolutionary incorporation of new neuron populations into preexisting circuitry.
Notes:
Itoh, Yasuhiro Sahni, Vibhu Shnider, Sara J McKee, Holly Macklis, Jeffrey D eng R01 NS049553/NS/NINDS NIH HHS/ R01 NS045523/NS/NINDS NIH HHS/ K12 HD093427/HD/NICHD NIH HHS/ F31 NS063516/NS/NINDS NIH HHS/ R01 NS104055/NS/NINDS NIH HHS/ R01 NS075672/NS/NINDS NIH HHS/ DP1 NS106665/NS/NINDS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2023/03/20 Cell Rep. 2023 Mar 28;42(3):112182. doi: 10.1016/j.celrep.2023.112182. Epub 2023 Mar 17.
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