Developmental and Repairing Production of Myelin: The Role of Hedgehog Signaling

Front. Cell. Neurosci., 2018 · DOI: 10.3389/fncel.2018.00305 · Published: September 6, 2018

Simple Explanation

The Sonic Hedgehog (Shh) protein plays a critical role in the development, maintenance, and repair of the central nervous system (CNS). One key function is in the generation of oligodendrocytes, which are responsible for myelinating axons in the CNS. Shh signaling is involved in the production of oligodendroglial cells in different areas of the developing brain and spinal cord, as well as in the repair of demyelinated lesions. Modulation of Hedgehog signaling can promote the repair of demyelinated lesions. Understanding the molecular mechanisms by which Shh controls oligodendrocyte production and myelination could lead to new therapeutic strategies for treating myelin diseases. A deeper understanding of the implication of each of the components that regulate oligodendrogenesis and myelination should beneﬁcially inﬂuence the therapeutic strategies in the ﬁeld of myelin diseases.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Shh signaling is necessary and sufficient for the expression of Olig1 and Olig2, transcription factors associated with oligodendrocyte development, in the developing neural tube.
2
In the spinal cord, floorplate-derived Hedgehog proteins are crucial for oligodendrocyte progenitor cell (OPC) specification, as demonstrated by the decrease in OPC markers in Shh-inactivated mice.
3
The Gli transcription factors, particularly Gli2, are involved in regulating the size and duration of the Olig1/2+ domain in the ventral neuroepithelium, influencing OPC development.

Research Summary

This mini-review focuses on the Shh-dependent molecular mechanisms involved in the spatial and temporal control of oligodendrocyte lineage appearance. The review highlights the intricate roles of Smoothened and Gli1, two essential components of Shh signaling, in postnatal myelin production and regeneration after demyelination. The authors suggest that a thorough determination of the molecular mechanisms and cell types targeted by pharmacological modulation of the Shh pathway components should improve our understanding and lead to new therapeutic approaches.

Practical Implications

Therapeutic Strategies for Myelin Diseases

A deeper understanding of Shh signaling components can inform the development of more effective treatments for myelin diseases.

Targeted Modulation of Shh Signaling

Precisely targeting Shh signaling pathways could enhance myelin repair and regeneration.

Understanding Gli1 Function

Further investigation into the dual role of Gli1 in NSC maintenance and differentiation is warranted for therapeutic potential.

Study Limitations

1
The antibodies used for visualizing Shh have actually recognized other members of the Hedgehog family.
2
Gli1 expression appears to be regulated in a complex manner depending on the animal model or the stage of the disease.
3
the phenotype of the cells expressing Gli1 or Smo is variable including NSCs, reactive astrocytes, oligodendroglial cells or even neurons for Gli1, microglia, oligodendroglial cells, and astrocytes for Smo.

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