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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Sonic hedgehog signaling in the postnatal brain.

Arturo Álvarez-Buylla1, Rebecca A Ihrie2

  • 1Department of Neurological Surgery, University of California - San Francisco, 35 Medical Center Way, San Francisco, CA 94143-0525, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California - San Francisco, 35 Medical Center Way, San Francisco, CA 94143-0525, USA.

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Sonic hedgehog (Shh) signaling remains active in the adult brain, influencing neural stem cell (NSC) renewal and repair. Research explores its roles beyond embryonic development, investigating its function in the mature central nervous system (CNS).

Keywords:
AstrocytesBrain tumor stem cellsNeural stem cellsPrimary ciliumReactive astrocytesSonic hedgehogStem cell microdomainsSubgranular zoneVentricular-subventricular zone

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Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Signaling

Background:

  • Sonic hedgehog (Shh) is a crucial morphogen in embryonic central nervous system (CNS) development, controlling cell proliferation, specification, and axonal guidance.
  • Shh acts as a mitogen for neural progenitor cells during embryonic development.
  • Emerging evidence indicates Shh signaling persists in the adult brain, prompting investigation into its functions in mature neural tissues.

Purpose of the Study:

  • To review the functional roles of Sonic hedgehog (Shh) signaling in the postnatal and adult brain.
  • To explore whether Shh signaling mechanisms in the adult CNS are similar to those in the embryonic CNS.
  • To highlight ongoing research into Shh ligand-producing cells and the regulation of Shh release in the adult brain.

Main Methods:

  • Review of existing literature on Shh signaling in embryonic, postnatal, and adult CNS.
  • Analysis of studies investigating Shh's role in neural stem cell (NSC) self-renewal and specification in adult germinal zones.
  • Examination of research on Shh's influence on astrocyte reactivity and brain injury response.

Main Results:

  • In adult brain germinal zones, Shh signaling modulates the self-renewal and specification of astrocyte-like progenitors (neural stem cells).
  • Shh signaling may influence the brain's response to injury, with proposed roles in enhancing or inhibiting reactive astrocyte development.
  • Adult germinal zones contain Shh-responsive cells, but the Shh ligand is not produced autonomously by these cells.

Conclusions:

  • Sonic hedgehog (Shh) signaling plays significant roles in the adult brain, particularly in neural stem cell regulation and response to injury.
  • Further research is needed to fully elucidate the sources of Shh ligand and the precise mechanisms governing its action in the mature CNS.
  • Understanding Shh's functions in the adult brain is critical for regenerative medicine and treating neurological disorders.