神経回路形成の発見が脊髄損傷・脳卒中治療への道を開く可能性(Discovery on neural wiring could unlock paths toward treatment of spinal cord injury, stroke)

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2026-09-16 ブラウン大学

ブラウン大学の研究チームは、発生過程にある神経細胞が軸索を正しい標的へ導く仕組みを明らかにした。従来は、軸索先端が周囲の環境を感知して進行方向を決めると考えられていたが、今回の研究では、**神経細胞体で遺伝子群を切り替える「遺伝的スイッチ」**が軸索誘導を制御することが示された。研究者らは脊髄の左右をつなぐ交連ニューロンを発生段階ごとに分離し、単一細胞RNAシーケンシングで遺伝子発現を解析。その結果、軸索が脊髄正中線を通過すると遺伝子発現が切り替わり、軸索先端に異なる誘導分子が現れて次の経路へ進むことが判明した。12,000個以上のニューロンの遺伝子発現情報から「遺伝的アトラス」も構築され、脊髄損傷や脳卒中後に軸索を正しい標的へ再生させる治療研究につながる可能性がある。現時点では基礎研究段階である。

神経回路形成の発見が脊髄損傷・脳卒中治療への道を開く可能性(Discovery on neural wiring could unlock paths toward treatment of spinal cord injury, stroke)
A cross section of the mouse embryonic spinal cord shows the green-highlighted axon guidance molecule L1, which is only expressed after the axons which connect the left and right sides of the central nervous system (shown here in red) have crossed the midline. Image courtesy of Alexander Jaworski.

<関連情報>

脊髄交連ニューロンの分化と正中線を越えた軸索成長を支える遺伝子発現プログラム Gene expression programs underlying spinal commissural neuron differentiation and axon growth across the midline

Jane R. Abolafia, Hanna Hameedy, Lakshmi Prakash, +3 , and Alexander Jaworski
Proceedings of the National Academy of Sciences  Published:September 15, 2026
DOI:https://doi.org/10.1073/pnas.2607727123

Abstract

Commissural neurons in the spinal cord project axons across the midline to fulfill various critical functions in somatosensory information processing and left–right coordination of motor output. These neurons have long served as a powerful model system for axon pathfinding, driving the identification of molecules and mechanistic principles for neuronal wiring that apply widely across neural circuits and model organisms. Aside from their shared initial projection path, commissural neurons are highly heterogenous, which has hampered lineage-based methods for accessing them, and most prior studies have been limited to small subpopulations of dorsal commissural neurons. The shared transcriptional programs for axonal midline crossing and the divergent gene expression signatures that define commissural neuron subtypes have therefore remained largely elusive. Here, we combine a genetic labeling strategy with single-cell RNA sequencing, birthdating, and complementary methods to study the production and transcriptomic trajectories of developing commissural neurons in the mouse embryonic spinal cord. We identify molecularly distinct commissural neuron subtypes that reveal stratification of this neuronal population beyond progenitor identities and temporal cohorts of neurogenesis, and we provide evidence that axon laterality is not linked to neuronal birthdate. We also uncover a large-scale gene expression switch that coincides with commissural axon growth across the midline and underlies differential axonal protein expression for guidance toward and away from the midline. Our findings elucidate both shared and subtype-specific gene expression programs that drive commissural neuron differentiation and axon midline crossing, and they provide a valuable resource for future studies of commissural neuron development and function.

細胞遺伝子工学
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