![]() These 12 mutants fell into 8 complementation groups, which we named dendritic arbor reduction ( dar) 1–8 ( Table 1). These neurons resemble mammalian neurons in morphological and cell biological features, such as multipolar morphology and the tapering of dendrites but not axons, making them a suitable model to study the differential development of dendrite and axon.įrom 3299 3 rd chromosomes carrying lethal mutations, we isolated 12 mutants that showed defects in dendritic but not axonal growth ( Figure 1A). ![]() We recently carried out a genetic screen to identify mutants with defects in dendritic and/or axonal development ( Grueber et al., 2007) by taking advantage of the highly specific marker for the class IV da neurons in Drosophila peripheral nervous system (PNS), pickpocket-EGFP ( ppk-EGFP) ( Grueber et al., 2003). We further show that such distinct sensitivity involves preferential reduction of membrane transport from soma to dendrites upon global reduction in ER-to-Golgi transport, and requirement of Golgi outposts for dendritic growth.ĭendritic and axonal growth exhibit distinct sensitivity to the reduction of ER-to-Golgi transport in da neurons in vivo Similar functions of Sar1 were observed in cultured mammalian neurons, corroborating the notion that dendritic and axonal growth exhibit distinct sensitivity to changes in ER-to-Golgi transport. Mosaic analysis revealed that these genes function cell-autonomously to regulate both dendritic growth and the secretory pathway. Strikingly, 3 of the 5 dar genes that we have so far identified molecularly encode critical regulators of the forward secretory pathway. Furthermore, whether dendritic Golgi outposts are required for dendritic growth and thus contribute to the generation of distinct dendrite and axon morphology is still unknown.įrom a large scale genetic screen by taking advantage of a highly specific marker for the class IV dendritic arborization (da) neurons in Drosophila, we isolated 8 complementation groups of dendritic arbor reduction ( dar) mutants, which share a common phenotype of reduced dendritic arbors but normal axonal growth. Whether the secretory pathway also plays a role in distinguishing the growth of dendrites and axons is an important open question. Recent findings suggest an active role of the polarized secretory trafficking in the formation of specific compartments of the dendritic arbors ( Horton et al., 2005). ![]() Golgi outpost has so far not been found in axons ( Horton and Ehlers, 2003), raising the question whether the polarized distribution of Golgi in neurons plays a role in the differential development of dendrites and axons. Unique to neurons is the presence of an additional satellite secretory pathway, including ER and Golgi outposts, in dendrites ( Aridor et al., 2004 Gardiol et al., 1999 Horton and Ehlers, 2003). The secretory pathway, which includes the endoplasmic reticulum (ER), Golgi complex, and post-Golgi intermediates ( van Vliet et al., 2003), is the major source of plasma membrane. It may also be important to regulate the membrane supply for dendrites and axons differently to establish their different morphology. Furthermore, the cytoskeleton regulators RhoA ( Lee et al., 2000) and MAP2 ( Harada et al., 2002) preferentially control dendritic growth. The cytoskeleton is organized differently in dendrites and axons ( Baas et al., 1988). The growth of dendrites and axons likely involves coordinated cytoskeletal reorganization and membrane trafficking ( Bradke and Dotti, 2000 Lecuit and Pilot, 2003). Little is known about how the structural differences between dendrites and axons are established. The distinct dependence between dendritic and axonal growth on the secretory pathway helps to establish different morphology of dendrites and axons.ĭendrites and axons, two major compartments of neurons, exhibit a number of morphological distinctions. We also show that dendritic growth is contributed by Golgi outposts, which are found predominantly in dendrites. Whereas limiting ER to Golgi transport resulted in decreased membrane supply from soma to dendrites, membrane supply to axons remained sustained. 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. We identified dar2, dar3, and dar6 genes as the homologs of Sec23, Sar1, and Rab1 of the secretory pathway. From a genetic screen, we isolated dendritic arbor reduction ( dar) mutants with reduced dendritic arbors but normal axons of Drosophila neurons. Little is known about how the distinct architectures of dendrites and axons are established.
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