Trends in Neurosciences
ReviewMoving around in a worm: netrin UNC-6 and circumferential axon guidance in C. elegans
Section snippets
UNC-6
Like most extracellular matrix and cell adhesion molecules, the UNC-6/netrin comprises multiple domains that are found in functionally divergent proteins. The UNC-6 VI and V domains are similar to the N-termini of subunits of laminin, which are phylogenetically conserved glycoprotein components of basement membranes [1]. The UNC-6 C domain is also conserved: it has been found in the complement C345 protein family, frizzled-related proteins, type-I-C-proteinase enhancer proteins (PCOLCE) and
Developing axon tracts
The patterning of axon tracts begins as neuronal growth cones from pioneer neurons are guided across the basal surface of the ectoderm. The expression of unc-6 by a set of epidermal cells precedes the first migrations [5]. Expression in these cells begins just before they form two symmetric rows on either side of the embryo. Expression continues as these cells slide over the neuroectoderm, and ends shortly after the cells meet at the ventral midline. At the end of this process, the neuroblasts
Dorsoventral positioning
Longitudinal nerves form at stereotyped dorsoventral positions as circumferentially migrating axons reach a position and turn in the longitudinal direction. Several observations suggest that the UNC-6 circumferential-guidance system can function independently of the system that guides longitudinal axon migration, and that a migrating axon is capable of responding to both systems. First, in unc-6 mutants, circumferential but not longitudinal migrations are disrupted [4]. Further, ectopic
Crossing the ventral midline
At the ventral midline, some axons cross and then turn longitudinally to make connections with axon tracts that develop on the other side of the body. The ventral nerve cord has two fascicles that flank the ventral midline (Fig. 4a). These axon tracts both run along an interface between the ventral epidermis and the ventral margin of the ventral sublateral muscle cells. Again, the dorsoventral position of these tracts appears to be determined by the combination of guidance molecules axons
Conclusions
In the nervous system, an intricate network of connections is made between neurons. These connections emerge as neuronal growth cones are directed through their environment by extracellular guidance molecules. Recent studies have implicated molecules as guidance cues or as receptors for such cues. In addition, some of the cytoplasmic signal transduction that underlies responses to these cues has also been revealed. Another achievement has been to understand better the manner by which guidance
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Cited by (55)
Mechanisms that regulate morphogenesis of a highly branched neuron in C. elegans
2019, Developmental BiologyCitation Excerpt :Additional genetic results confirmed that UNC-6/Netrin and its receptor UNC-40/DCC are also required for the wild-type complement of 20 branches (Smith et al., 2010) and function in a common pathway with UNC-52/Perlecan and NID-1/Nidogen (Celestrin et al., 2018). UNC-6/Netrin is secreted from ventrally-positioned cells to direct the dorsal trajectory of motor neuron axons by interacting with the UNC-40/DCC receptor (Wadsworth, 2002). However, PVD-specific expression of UNC-40/DCC rescues PVD 20 branching defects suggesting that UNC-40/DCC may drive 20 branch outgrowth by responding to an UNC-6/Netrin signal anchored to the basal lamina by UNC-52/Perlecan and NID-1/Nidogen (Celestrin et al., 2018).
The dendritic tree and brain disorders
2012, Molecular and Cellular NeuroscienceCitation Excerpt :Different extracellular cues, including those that induce neuronal activity, neurotrophins, cell adhesion molecules, and extracellular guidance molecules, influence dendrite morphology and branching and development (Van Aelst and Cline, 2004). Specific factors that govern the process of dendrite morphogenesis include neurotransmitters (Kaufmann and Moser, 2000), netrins (Wadsworth, 2002) semaphorins (Dent et al., 2004; Polleux et al., 2000), and molecules, such as Notch1 and Slits (Franklin et al., 1999; McAllister et al., 1996, 1997; McAllister et al., 1995; Redmond and Ghosh, 2001; Redmond et al., 2000; Salama-Cohen et al., 2006; Salama-Cohen et al., 2005; Whitford et al., 2002) and brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) (Bosco and Linden, 1999; Danzer et al., 2008; Dijkhuizen and Ghosh, 2005; Niblock et al., 2000). In addition, transcription factors, such as Cux1 and Cux2, regulate dendrite branching, spine development, and synapse formation in layers II–III of the cerebral cortex (Cubelos et al., 2010; Li et al., 2010).
The thrombospondin repeat containing protein MIG-21 controls a left-right asymmetric Wnt signaling response in migrating C. elegans neuroblasts
2012, Developmental BiologyCitation Excerpt :Apart from the two TSP-I repeats, sequence similarity searches did not reveal other conserved domains in MIG-21 and no orthologs were found outside the nematode phylum. Although MIG-21 shares a TSP-I motif with UNC-5, a receptor that functions together with UNC-40/DCC in UNC-6/Netrin signaling (Wadsworth, 2002), our results indicate that mig-21 and unc-40 function in parallel genetic pathways in Q neuroblast polarization and migration. To examine the expression pattern of mig-21, we used single molecule mRNA FISH (smFISH) (Raj et al., 2008) to quantitatively determine mig-21 transcript localization and levels in L1 stage larvae.
TOM-1/tomosyn acts with the UNC-6/netrin receptor UNC-5 to inhibit growth cone protrusion in Caenorhabditis elegans
2023, Development (Cambridge)