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Sonic Hedgehog signalling in the developing and adult brain
Dorota Charytoniuk1, Betina Porcel, José Rodríguez Gomez
1Laboratoire de Neurobiologie Cellulaire et Moléculaire, Centre National de la Recherche Scientifique, 91198, Gif-sur-Yvette, France
Journal of Physiology, Paris
|January 5, 2002
Summary
Sonic Hedgehog (Shh) signaling is crucial for embryonic development and also plays roles in the postnatal and adult brain. Modified Shh peptides enhance neuroblast proliferation, suggesting new therapeutic potential.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Sonic Hedgehog (Shh) is a secreted polypeptide family vital for embryonic development.
- Shh signaling involves Patched (Ptc) and Smoothened (Smo) receptors, activating Gli transcription factors.
- Shh exhibits inductive, proliferative, neurotrophic, and neuroprotective effects on neural cells.
Purpose of the Study:
- To investigate the distribution of Shh signaling genes in embryonic and adult rat brains.
- To explore the pharmacological properties of Shh peptides.
- To elucidate the roles of Shh signaling beyond early embryonic development.
Main Methods:
- Gene distribution analysis in rat embryos and adults.
- In vitro cell culture of rat cerebellar granule cell neuroblasts.
- [3H]thymidine incorporation assays to measure cell proliferation.
- Analysis of Patched (Ptc) protein's sterol sensing domain.
Main Results:
- Shh, Ptc, and Smo distribution aligns with the functional model in the ventral neural tube.
- Myristoylated ShhN (myrShhN) significantly enhances neuroblast proliferation compared to ShhN.
- Ptc and Smo transcripts colocalize in specific adult brain areas, but Ptc can be expressed without Smo.
Conclusions:
- Shh signaling pathways are active in the postnatal and adult brain, with potential roles beyond embryonic development.
- Amino-terminal lipid modification is critical for ShhN's biological activity.
- Shh may signal through Ptc/Smo complexes or Ptc alone in the adult brain.