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Shh-proteoglycan interactions regulate maturation of olfactory glomerular circuitry.
Laura Persson1, Rochelle M Witt, Meghan Galligan
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Neurobiology, Harvard Medical School, Boston, Massachusetts.
Developmental Neurobiology
|June 11, 2014
Summary
Sonic Hedgehog (Shh) signaling is crucial for maintaining olfactory glomerular circuitry and neurogenesis. Impaired Shh binding disrupts olfactory sensory neuron connections, leading to smaller olfactory bulbs and reduced neuron development.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- The olfactory system requires precise connections between olfactory sensory neurons (OSNs) and olfactory bulb (OB) neurons for odor processing.
- The mechanisms governing the formation and maintenance of this glomerular circuitry are not fully understood.
Purpose of the Study:
- To investigate the role of Sonic Hedgehog (Shh) signaling in the refinement and maintenance of olfactory glomerular circuitry.
- To understand how Shh interacts with proteoglycan co-receptors in olfactory system development.
Main Methods:
- Utilized genetically modified mice (Shh(Ala/Ala)) with impaired Shh binding to proteoglycan co-receptors.
- Examined olfactory bulb size, glomerular number, and the correspondence between olfactory receptors and glomeruli.
- Assessed neurogenesis in the subventricular zone (SVZ) and the development of periglomerular cells.
Main Results:
- Shh(Ala/Ala) mice displayed smaller olfactory bulbs with fewer glomeruli and a loss of specific olfactory receptor-to-glomerulus mapping.
- Deficits in synaptic pruning within the OB were observed in mutant animals.
- Mature mutant mice showed reduced proliferation and neurogenesis in the SVZ, particularly affecting calbindin-expressing periglomerular cells.
Conclusions:
- Shh signaling, via interactions with proteoglycan co-receptors, is essential for multiple stages of olfactory system development.
- This signaling pathway regulates neurogenesis and ensures the precise wiring of olfactory neuronal circuitry for proper function.
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