No abstract

Disruptions in neuronal dendrite development alter brain circuitry and are associated with debilitating neurological disorders. Nascent apical dendrites of cortical excitatory neurons project into the marginal zone (MZ), a cell-sparse layer characterized by intense chondroitin sulfate proteoglycan (CSPG) expression. Paradoxically, CSPGs are known to broadly inhibit neurite growth and regeneration. This raises the possibility that the growing apical dendrite is Significance Statement Appropriate dendritic development is essential for normal neuronal function throughout life. The area where most cortical dendrites initially project (the marginal zone) is cell sparse but highly enriched in chondroitin sulfate proteoglycans (CSPGs). While CSPGs are known to inhibit axonal outgrowth, their impact on dendritic growth is unclear. This study demonstrates that the growth of the apical dendrite is also inhibited by CSPGs. However, this inhibitory effect can be reversed by chondroitinase treatment and by activation of the Reelin signaling pathway. Disruptions in Reelin signaling cause intellectual disability and have been linked to autism. Thus, these findings identify a context in which Reelin signaling operates and provide insight into the underlying mechanism of neurodevelopmental disorders.