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Synaptic Hyaluronan Synthesis and CD44-Mediated Signaling Coordinate Neural Circuit Development
1Department of Anatomy and Cell Biology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Cells
|October 23, 2021
Summary
Hyaluronan (HA) influences early neural circuit formation by regulating synapse development. Increased HA synthesis reduces excitatory connections and promotes inhibitory ones, impacting neural activity.
Area of Science:
- Neuroscience
- Developmental Biology
- Extracellular Matrix Biology
Background:
- Hyaluronan (HA) forms perineuronal nets around inhibitory neurons postnatally.
- The role of HA in initial neural circuit formation is unclear.
- HA is present in the synaptic cleft of developing excitatory synapses.
Purpose of the Study:
- To investigate the mechanisms regulating HA synthesis and signaling during synapse formation.
- To understand HA's role in early neural circuit development.
Main Methods:
- Utilized human cortical spheroids and neonatal mouse brain models.
- Investigated the function of hyaluronan synthase-2 (HAS2) and the HA receptor CD44.
- Analyzed effects on synaptogenesis and action potential formation.
Main Results:
- HAS2 overexpression increases HA levels in developing neural circuits.
- Elevated HA reduces excitatory synaptogenesis and promotes inhibitory synaptogenesis.
- CD44 mediates HA retention and suppresses excitatory synaptogenesis via RhoGTPase signaling.
Conclusions:
- HA synthesis, retention, and signaling are regulated during neural circuit development.
- Altered HA levels can contribute to synaptic defects relevant to neurological disorders.
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