Molecules and mechanisms of dendrite development in Drosophila

Abstract

Neurons are one of the most morphologically diverse cell types, in large part owing to their intricate dendrite branching patterns. Dendrites are structures that are specialized to receive and process inputs in neurons, thus their specific morphologies reflect neural connectivity and influence information flow through circuits. Recent studies in Drosophila on the molecular basis of dendrite diversity, dendritic guidance, the cell biology of dendritic branch patterning and territory formation have identified numerous intrinsic and extrinsic cues that shape diverse features of dendrites. As we discuss in this review, many of the mechanisms that are being elucidated show conservation in diverse systems.

Fig. 1.

Diverse morphologies of Drosophila dendrites. (A) A Drosophila RP2 motoneuron projects its dendritic arbor within the ventral nerve cord of the embryonic CNS. Adapted with permission from Ou et al. (Ou et al., 2008). Yellow arrows indicate dendrites, yellow arrowheads indicate axons, and cell bodies are indicated by white arrowheads in this and subsequent panels. (B) The dendrites of a highly branched class IV dendritic arborization (da) neuron of a third-instar Drosophila larva. Image reproduced with permission from Matthews et al. (Matthews et al., 2007). (C) Schematic of a Drosophila larva showing the location of da neurons in the peripheral nervous system (PNS) and motoneuron cell bodies (red) within the central nervous system (CNS) (not all segments or cells are shown). Anterior is to the left and dorsal is up. (D) A mushroom body neuron (green) elaborates dendrites near the cell body. Image reproduced with permission from Zhu et al. (Zhu, S. et al., 2006). (E) A single projection neuron projects its dendrites to a single glomerulus (outlined in yellow) within the antennal lobe (magenta). Image reproduced with permission from Komiyama and Luo (Komiyama and Luo, 2007). Scale bars: 10 μm in A; 50 μm in B,E; 20 μm in D.

Fig. 2.

Organelle trafficking and dendrite morphogenesis. (A) Schematic of Golgi distribution in Drosophila da neurons. Golgi outposts are localized to dendritic branch points and excluded from the axon. The predominant minus-end distal arrangement of microtubules in these dendrites is also shown. (B-E) Dendritic morphologies of wild-type and mutant class IV Drosophila da neurons. Arrows indicate dendrites. (B) Tracing of a wild-type class IV da neuron. (C) Tracing of a sar1 mutant class IV da neuron that shows reduced branch complexity. Sar1 is involved in the formation of COPII vesicles during trafficking from ER to the Golgi. (D) Tracing of a class IV da neuron with a mutation in dynein light intermediate chain (Dlic2) showing reduced dendrite length and redistribution of branches to areas nearer to the cell body (shown in black). Dlic2 is a component of the dynein complex, a minus-end-directed microtubule motor. (E) Tracing of a class IV da neuron expressing a dominant-negative Rab5 [Rab5(S43N)]. Dominant-negative Rab5 abrogates the proximal hyperbranching phenotype of Dlic2 mutations. Rab5 is a GTPase that functions in early endocytosis. Tracings in B,C adapted with permission from Ye et al. (Ye et al., 2007). Tracings in D,E adapted with permission from Satoh et al. (Satoh et al., 2008). Scale bars: 75 μm.

Fig. 3.

Diversity of da neuron morphology and transcription factor expression. (A-D) Dendritic arbors of class I, II, III and IV da neurons (left to right). Arrowheads indicate regions of arbors that exemplify class-specific branching complexity. Cells are classified according to increasing arbor complexity. The expression status of transcription factors Cut, Knot, Abrupt and Spineless is listed below each morphological class. Filled boxes indicate expression, white boxes indicate no detectable expression. Progressively higher levels of Cut expression are indicated by progressively darker shadings (the degree of shading is not intended to indicate relative levels among the different transcription factors). Images in A-C reproduced with permission from Matthews et al. (Matthews et al., 2007). Scale bar: 50 μm.

Fig. 4.

Transcriptional control of dendritic targeting in the Drosophila antennal lobe. (A) Schematic organization of the Drosophila antennal lobe (AL). For simplicity, only a subset of glomeruli are shown. Projection neurons (PNs) from anterodorsal (adPNs, red), lateral (lPNs, blue) and ventral (vPNs, green) lineages project dendrites to glomeruli where they connect with olfactory receptor neuron (ORN) axons (a vPN projection is not shown here). PN axons extend to higher-order olfactory centers in the brain. Transcription factors discussed in this review are shown. The schematic of glomerular organization is based on data from Couto et al. and is adapted with permission (Couto et al., 2005). (isl is also known as tup - Flybase.) (B-Cd) Cell-autonomous alterations in transcription factor expression redirect dendrite targeting. (B) Wild-type DL1 adPN (red) dendrites normally target to the DL1 glomerulus (shaded in red in the AL). adPNs express acj6 but not drifter or cut. (Ca-Cd) Dendrite targeting of genetically manipulated DL1 adPNs. (Ca) acj6 mutants extend dendrites outside their normal glomerulus. (Cb) acj6 mutant DL1 adPNs forced to express Drifter partially mistarget to more anterior glomeruli. (Cc) acj6 mutant DL1 adPNs forced to express Cut target medial adPN glomeruli. (Cd) Expression of both Drifter and Cut in acj6 mutant DL1 adPNs results in mistargeting of dendrites to medial lPN glomeruli. Schematic based on published data (Komiyama et al., 2003; Komiyama and Luo, 2007).

Fig. 5.

Graded expression of Sema-1a directs projection neuron dendrite targeting. (A) Projection neurons (PNs) that express the highest levels of Sema-1a (red) form protoglomeruli at the most dorsolateral (DL) regions of the Drosophila antennal lobe (AL), whereas those that express lower levels target to more ventromedial (VM) regions (orange and yellow). (B) Olfactory receptor neuron (ORN) axons (not shown) and PN dendrites coalesce into mature glomeruli through axon-dendrite and dendrite-dendrite interactions (see text). Manipulation of Sema-1a levels in PNs causes autonomous switches in dendrite targeting [see text and Komiyama et al. (Komiyama et al., 2007)]. Adapted with permission from Komiyama et al. (Komiyama et al., 2007).

Fig. 6.

Role of Dscam in dendrite self-avoidance. (Aa) Schematic of a wild-type projection neuron (PN) targeting the DL1 glomerulus in the Drosophila antennal lobe. Dendrites project throughout the entire glomerulus (red). (Ab) In a Dscam mutant DL1 clone, dendrites fail to completely innervate their target glomerulus (coverage area in red). Schematic based on published data (Zhu, H. et al., 2006). (Ba-Bd) Dscam control of self-avoidance in Drosophila da neurons. Schematic of two da neurons and their dendritic arbors (green and pink). (Ba) In a wild-type da neuron, dendrites of each cell self-avoid, but overlap with non-sister dendrites. Isoneuronal refers to the behavior of dendrites from the same cell (sister dendrites) and heteroneuronal refers to the behavior of dendrites from different cells. (Bb-Bd) Schematics of dendritic phenotypes observed in Dscam mutant animals. (Bb) In a Dscam mutant, the dendrites of each cell fail to self-avoid and overlap extensively throughout their arbors. (Bc) Single isoforms expressed in one Dscam mutant cell (green) rescue self-avoidance. (Bd) Overexpression of a single isoform in two cells with dendrites that normally overlap leads to repulsion between branches (heteroneuronal avoidance). Schematics based on published data (Hughes et al., 2007; Matthews et al., 2007; Soba et al., 2007).