Sonic Hedgehog Signaling in the Postnatal Brain

Semin Cell Dev Biol, 2014 · DOI: 10.1016/j.semcdb.2014.05.008 · Published: September 1, 2014

Simple Explanation

Sonic hedgehog (Shh) signaling plays a critical role in the developing central nervous system (CNS) by influencing cell proliferation, specialization, and axon targeting. In the adult brain, Shh signaling continues to be important in the two major germinal zones where it modulates the self-renewal and specification of neural stem cells. Shh signaling may also play a role in how the mature brain responds to injury by either promoting or inhibiting the development of reactive astrocytes.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Not specified

Key Findings

1
Shh signaling is essential for the establishment and maintenance of adult neural stem cell niches in the ventricular-subventricular zone (V-SVZ) and subgranular zone (SGZ).
2
In the adult brain, the Shh ligand is primarily produced by mature neurons, which contrasts with the embryonic brain where production is more widespread.
3
In differentiated astrocytes, Shh signaling restrains them from becoming reactive, except in cases of brain injury where Shh production by reactive astrocytes may enhance the glial phenotype.

Research Summary

Sonic hedgehog (Shh) is a key factor in the developing central nervous system (CNS), influencing proliferation, specification, and axonal targeting. Shh signaling modulates the self-renewal and specification of astrocyte-like primary progenitors, frequently referred to as neural stem cells (NSCs), in the two major germinal zones of the adult brain. The Shh pathway is also implicated in brain tumor development, where it may maintain the tumor-propagating "brain tumor stem cell" population.

Practical Implications

Targeted Therapies for Brain Tumors

Inhibition of Shh signaling can suppress glioma cell propagation, suggesting potential therapeutic strategies for brain tumors.

Understanding Adult Neurogenesis

Further research into Shh's role in adult neurogenesis could lead to interventions that enhance neural repair and regeneration.

Modulating Reactive Astrogliosis

Manipulating Shh signaling could provide a means to control reactive astrogliosis, potentially improving outcomes after brain injury.

Study Limitations

1
The conditions that trigger Shh ligand release in the adult brain are not fully understood.
2
The mechanism for transport of Shh to responsive cells in the adult brain remains to be fully defined.
3
The specific roles of Shh in response to different types of brain injury require further investigation.

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