Spontaneously Regenerative Corticospinal Neurons in Mice
type: CreativeWork
description: The mammalian spinal cord receives input from the motor cortex via the corticospinal tract (CST). The CST comprises corticospinal neuron (CSN) axons that begin in Layer 5b of motor cortex and can extend up to one meter to reach targets in the caudal spinal cord in humans. CSNs regulate the spinal cord's sensorimotor function; however, the extent of their impact on motor control differs between species. In macaques, lesion of the pyramidal tract produces immediate limb paralysis. In rodents, their genetic ablation profoundly impacts skilled-reaching ability but does not produce paralysis. In almost all examined mammals, corticospinal axons primarily terminate contralateral to their cell bodies of origin. Despite the predominance of contralateral CSN termination, a minority of CSN axons terminate ipsilaterally. There has been considerable examination of ipsilateral axons in unilateral cortical injury because of evidence that they are a potential circuit for the uninjured cortex to compensate for the damaged one. However, little is known about their anatomy and function in healthy animals. Though sparse, these ipsilateral axons are a remarkable deviation from the norm. Brains have evolved only in bilaterally symmetric animals, so the midline is a foundational architectural principle of all central nervous systems. Accordingly, an intricate and redundant ensemble of molecular signals exerts tight control over midline crossing. The ipsilateral axons represent a consistent anomaly across many species at an evolutionarily ancient midline boundary that is under strict developmental control. To better understand these ipsilateral axons, we first sought to characterize their anatomy with a diverse array of emerging methods in mouse molecular neuroscience. Using anterograde tracing methods, tissue clearing, and Smart-seq3 single-nucleus RNA-sequencing (snRNA-seq), we found that ipsilateral CSN axons project to regions of the ventral horn, including directly to motor neurons. B…
abstract: The mammalian spinal cord receives input from the motor cortex via the corticospinal tract (CST). The CST comprises corticospinal neuron (CSN) axons that begin in Layer 5b of motor cortex and can extend up to one meter to reach targets in the caudal spinal cord in humans. CSNs regulate the spinal cord's sensorimotor function; however, the extent of their impact on motor control differs between species. In macaques, lesion of the pyramidal tract produces immediate limb paralysis. In rodents, their genetic ablation profoundly impacts skilled-reaching ability but does not produce paralysis. In almost all examined mammals, corticospinal axons primarily terminate contralateral to their cell bodies of origin. Despite the predominance of contralateral CSN termination, a minority of CSN axons terminate ipsilaterally. There has been considerable examination of ipsilateral axons in unilateral cortical injury because of evidence that they are a potential circuit for the uninjured cortex to compensate for the damaged one. However, little is known about their anatomy and function in healthy animals. Though sparse, these ipsilateral axons are a remarkable deviation from the norm. Brains have evolved only in bilaterally symmetric animals, so the midline is a foundational architectural principle of all central nervous systems. Accordingly, an intricate and redundant ensemble of molecular signals exerts tight control over midline crossing. The ipsilateral axons represent a consistent anomaly across many species at an evolutionarily ancient midline boundary that is under strict developmental control. To better understand these ipsilateral axons, we first sought to characterize their anatomy with a diverse array of emerging methods in mouse molecular neuroscience. Using anterograde tracing methods, tissue clearing, and Smart-seq3 single-nucleus RNA-sequencing (snRNA-seq), we found that ipsilateral CSN axons project to regions of the ventral horn, including directly to motor neurons. B…
author: Fait, Benjamin William
keywords: corticospinal neurons, ipsilateral projections, motor cortex, spinal cord, axon regeneration, molecular profiling, Life Sciences
date published: 2025-01-01T08:00:00Z
date modified: 2026-07-24T04:11:28Z
provider: Rockefeller
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Rockefeller