New perspectives on the mechanisms establishing the dorsal-ventral axis of the spinal cord

Curr Top Dev Biol, 2019 · DOI: 10.1016/bs.ctdb.2018.12.010 · Published: January 1, 2019

Regenerative Medicine Neurology Genetics

Simple Explanation

The spinal cord has distinct regions along its dorsal-ventral axis, each responsible for different functions. Motor control neurons are in the ventral horn, while sensory neurons are in the dorsal horn. The ventral spinal cord is primarily patterned by sonic hedgehog (Shh), which acts as a morphogen, meaning it directs cell fate based on its concentration. In contrast, the dorsal spinal cord is patterned by multiple factors, including BMPs and Wnts. Unlike Shh, BMPs don't act as morphogens but have signal-specific activities.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
The ventral spinal cord is patterned by Shh, which acts as a morphogen in a concentration-dependent manner.
2
BMPs in the dorsal spinal cord do not act as morphogens; instead, each BMP has signal-specific activities, directing a unique range of dorsal cellular identities.
3
Wnt signaling in the dorsal spinal cord primarily acts as a mitogen, regulating cell proliferation, though it may also have patterning activities.

Research Summary

The dorsal-ventral axis of the spinal cord is crucial for segregating neurons according to function, with motor neurons in the ventral horn and sensory interneurons in the dorsal horn. Ventral patterning is primarily governed by the morphogen Shh, while dorsal patterning involves multiple BMP and Wnt factors, with BMPs exhibiting signal-specific rather than morphogenic activity. Understanding these developmental mechanisms is promising for neural repair, particularly in generating specific neuronal populations from pluripotent stem cells for cellular replacement therapies in spinal cord injuries.

Practical Implications

Stem Cell Therapies

Knowledge of spinal cord development allows for the generation of specific neuronal populations from pluripotent stem cells, offering potential treatments for spinal cord injuries.

Drug Screening

Pluripotent stem cells are a powerful reagent for understanding disease mechanisms and serving as a platform for drug screening.

Understanding Disease

Stem cell-derived MNs have provided a critical window into understanding of the pathology of motor diseases, including amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA).

Study Limitations

1
Directed differentiation protocols for sensory spinal relay INs from PSCs is lacking.
2
PSC-derived MNs and dorsal INs arise as mixed populations, with varied efficiencies in the current protocols.
3
More studies also need to be performed to evaluate the ability to incorporate into the injured spinal cord of adult animal, form synaptic connections and provide functional recovery.

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