Impaired dendritic spine development in a zebrafish model of Fragile X

Dendritic spines are the principal site of excitatory synapse formation in the human brain. Impaired formation of spines during development has been observed in several autism spectrum disorders (ASDs), including Fragile X syndrome. Fragile X is caused by transcriptional silencing of the Fmr1 gene encoding the RNA-binding protein FMRP (Fragile X mental retardation protein). While spine development has been well characterized in the mammalian CNS, spines are not unique to mammals. Pyramidal neurons (PyrNs) of the zebrafish optic tectum form an apical dendrite containing a dense array of dendritic spines. We employed a genetic labeling system to monitor PyrN dendritic spine development in larval zebrafish. Our findings identify a developmental window when PyrN dendrite growth is concurrent with spine formation. Throughout this period, motile, transient filopodia gradually transform into stable spines containing postsynaptic specializations. fmr1 mutant zebrafish larvae exhibit pronounced defects in both PyrN dendrite growth and the formation of morphologically mature spines. Live imaging of PyrN dendrites suggests these defects are caused by an inability to stabilize nascent contacts. These findings indicate spine stabilization is essential for PyrN dendritic arborization and establish zebrafish larvae as a model system to study spine development in vivo .