The role of the secretory pathway in dendrite and axon development

The secretory pathway supplies membrane proteins and lipids essential for cell growth. The development of neuronal dendrites and axons requires large amount of membrane molecules transported by the secretory pathway. However, little is known about the role of the secretory pathway in establishing the architectures of dendrites and axons. From a genetic screen, we isolated dendritic arbor reduction (dar) mutants with reduced dendritic arbors but normal axons of Drosophila neurons. We identified dar2, dar3, and dar6 genes as the homologs of Sec23, Sar1, and Rab1 of the secretory pathway. In both Drosophila and rodent neurons, defects in Sar1 expression preferentially affected dendritic growth, revealing evolutionarily conserved difference between dendritic and axonal development in the sensitivity to limiting membrane supply from the secretory pathway. Whereas limiting ER-to-Golgi transport resulted in decreased membrane supply from soma to dendrites, membrane supply to axons remained sustained. We also show that dendritic growth is contributed by Golgi outposts, which are found predominantly in dendrites. We found that dendritic Golgi outposts are at least in part generated in the soma, excluded from the axon by dynein based transport, and distributed in neuron type specific patterns. Furthermore, we found that a trans-Golgi network localized regulator of secretory trafficking, Rab6, has important roles in dendrite morphogenesis