Nonautonomous Roles of MAB-5/Hox and the Secreted Basement Membrane Molecule SPON-1/F-Spondin in <i>Caenorhabditis elegans</i> Neuronal Migration

Josephson, Matthew P.; Miltner, Adam M.; Lundquist, Erik A.

doi:10.1534/genetics.116.188367

Cited by 15 publications

(20 citation statements)

References 65 publications

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“…While the transmembrane receptors UNC-40/DCC and PTP-3/LAR act as guidance receptors in Q cells, no extracellular factor has been identified that controls the direction of Q migration. Body wall muscle cells produce SPON-1/F-spondin and a signal dependent upon NFM-1/Merlin, both of which control the protrusive ability of the Q cells but do not affect direction [ 12 , 13 ]. Wnt ligands control Q descendant migrations [ 14 , 15 , 16 ] but do not apparently affect initial Q protrusion and migration.…”

Section: Introductionmentioning

confidence: 99%

The Collagens DPY-17 and SQT-3 Direct Anterior–Posterior Migration of the Q Neuroblasts in C. elegans

Lang

Lundquist

2021

JDB

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Cell adhesion molecules and their extracellular ligands control morphogenetic events such as directed cell migration. The migration of neuroblasts and neural crest cells establishes the structure of the central and peripheral nervous systems. In C. elegans, the bilateral Q neuroblasts and their descendants undergo long-range migrations with left/right asymmetry. QR and its descendants on the right migrate anteriorly, and QL and its descendants on the left migrate posteriorly, despite identical patterns of cell division, cell death, and neuronal generation. The initial direction of protrusion of the Q cells relies on the left/right asymmetric functions of the transmembrane receptors UNC-40/DCC and PTP-3/LAR in the Q cells. Here, we show that Q cell left/right asymmetry of migration is independent of the GPA-16/Ga pathway which regulates other left/right asymmetries, including nervous system L/R asymmetry. No extracellular cue has been identified that guides initial Q anterior versus posterior migrations. We show that collagens DPY-17 and SQT-3 control initial Q direction of protrusion. Genetic interactions with UNC-40/DCC and PTP-3/LAR suggest that DPY-17 and SQT-3 drive posterior migration and might act with both receptors or in a parallel pathway. Analysis of mutants in other collagens and extracellular matrix components indicated that general perturbation of collagens and the extracellular matrix (ECM) did not result in directional defects, and that the effect of DPY-17 and SQT-3 on Q direction is specific. DPY-17 and SQT-3 are components of the cuticle, but a role in the basement membrane cannot be excluded. Possibly, DPY-17 and SQT-3 are part of a pattern in the cuticle and/or basement membrane that is oriented to the anterior–posterior axis of the animal and that is deciphered by the Q cells in a left–right asymmetric fashion. Alternatively, DPY-17 and SQT-3 might be involved in the production or stabilization of a guidance cue that directs Q migrations. In any case, these results describe a novel role for the DPY-17 and SQT-3 collagens in directing posterior Q neuroblast migration.

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Section: Introductionmentioning

confidence: 99%

The Collagens DPY-17 and SQT-3 Direct Anterior–Posterior Migration of the Q Neuroblasts in C. elegans

Lang

Lundquist

2021

JDB

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“…Our combined results here suggest that NFM-1 and SLT-1 might act in the body wall muscles and/or anal sphincter muscle. Of note, the Q-cell protrusions are in close proximity to body wall muscles (Figure 6), and the posterior body wall muscles are the source of SPON-1/ F-spondin, which is involved in Q migrations (Josephson et al 2016b). Possibly, the posterior body wall muscles surrounding the Q neuroblasts serve as a source for cues that promote and guide their migrations.…”

Section: Discussionmentioning

confidence: 99%

“…Although numerous molecules have been identified that act in the Q cells to promote migration, such as the transmembrane receptors UNC-40/DCC, PTP-3/ LAR, and MIG-13 (Sundararajan and Lundquist 2012;Wang et al 2013;Sundararajan et al 2015), fewer have been identified that act outside the Q cells to control their migration. Of the nonautonomous genes that have been implicated in Q-descendant migration, most are secreted molecules such as Wnts (Hunter et al 1999;Whangbo and Kenyon 1999;Korswagen 2002;Pan et al 2006) and SPON-1/F-spondin (Josephson et al 2016b), although the Fat-like cadherin CDH-4 has been demonstrated to nonautonomously affect Q-cell migration (Sundararajan et al 2014).…”

Section: Discussionmentioning

confidence: 99%

The Caenorhabditis elegans NF2/Merlin Molecule NFM-1 Nonautonomously Regulates Neuroblast Migration and Interacts Genetically with the Guidance Cue SLT-1/Slit

Josephson¹,

Aliani²,

Norris³

et al. 2017

Genetics

Self Cite

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During nervous system development, neurons and their progenitors migrate to their final destinations. In Caenorhabditis elegans, the bilateral Q neuroblasts and their descendants migrate long distances in opposite directions, despite being born in the same posterior region. QR on the right migrates anteriorly and generates the AQR neuron positioned near the head, and QL on the left migrates posteriorly, giving rise to the PQR neuron positioned near the tail. In a screen for genes required for AQR and PQR migration, we identified an allele of nfm-1, which encodes a molecule similar to vertebrate NF2/Merlin, an important tumor suppressor in humans. Mutations in NF2 lead to neurofibromatosis type II, characterized by benign tumors of glial tissues. Here we demonstrate that in C. elegans, nfm-1 is required for the ability of Q cells and their descendants to extend protrusions and to migrate, but is not required for direction of migration. Using a combination of mosaic analysis and cell-specific expression, we show that NFM-1 is required nonautonomously, possibly in muscles, to promote Q lineage migrations. We also show a genetic interaction between nfm-1 and the C. elegans Slit homolog slt-1, which encodes a conserved secreted guidance cue. Our results suggest that NFM-1 might be involved in the generation of an extracellular cue that promotes Q neuroblast protrusion and migration that acts with or in parallel to SLT-1. In vertebrates, NF2 and Slit2 interact in axon pathfinding, suggesting a conserved interaction of NF2 and Slit2 in regulating migratory events.

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“…2016a), they do not control initial direction of Q migration. SPON-1/F-spondin and a signal produced in muscles by NFM-1/Merlin that interacts with SLT-1/Slit control the ability of Q cells to migrate, but are not involved in direction of migration (J osephson et al . 2016b; J osephson et al .…”

Section: Discussionmentioning

confidence: 99%

“…While the transmembrane receptors UNC-40/DCC and PTP-3/LAR act in Q cells as guidance receptors, no extracellular factor has been identified that controls the direction of Q migration. Body wall muscle cells produce SPON-1/F-spondin and a signal dependent upon NFM-1/Merlin, both of which control the protrusive ability of the Q cells but do not affect direction (J osephson et al . 2016b; J osephson et al .…”

Section: Introductionmentioning

confidence: 99%

The Collagens DPY-17 and SQT-3 Direct Anterior-Posterior Migration of the Q Neuroblasts inC. elegans

Lang

Lundquist

2021

Preprint

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Cell adhesion molecules and their extracellular ligands control morphogenetic events such as directed cell migration. The migration of neuroblasts and neural crest cells establishes the structure of the central and peripheral nervous systems. In C. elegans, the bilateral Q neuroblasts and their descendants undergo long-range migrations with left/right asymmetry. QR and descendants on the right migrate anteriorly, and QL and descendants on the left migrate posteriorly, despite identical patterns of cell division, cell death, and neuronal generation. The initial direction of protrusion of the Q cells relies on the left/right asymmetric function of the transmembrane receptors UNC-40/DCC and PTP-3/LAR in the Q cells. Here we show that Q cell left/right asymmetry of migration is independent of the GPA-16/Galpha pathway that regulates other left/right asymmetries including nervous system L/R asymmetry. No extracellular cue has been identified that guides initial Q anterior versus posterior migration. We show that the Collagens DPY-17 and SQT-3 control initial Q direction of protrusion. Genetic interactions with UNC-40/DCC and PTP-3/LAR suggest that DPY-17 and SQT-3 drive posterior migration and might act with both receptors or in a parallel pathway. Analysis of mutants in other Collagens and extracellular matrix components indicated that general perturbation of Collagens and the ECM did not result in directional defects, and that the effect of DPY-17 and SQT-3 on Q direction is specific. DPY-17 and SQT-3 are components of the cuticle, but a role in the basement membrane cannot be excluded. Possibly, DPY-17 and SQT-3 are part of a pattern in the cuticle and/or basement membrane that is oriented to the anterior-posterior axis of the animal and that is deciphered by the Q cells in a left-right asymmetric fashion. Alternatively, DPY-17 and SQT-3 might be involved in the production or stabilization of a guidance cue that directs Q migrations. In any case, these results describe a novel role for the DPY-17 and SQT-3 Collagens in directing posterior Q neuroblast migration.

show abstract

Nonautonomous Roles of MAB-5/Hox and the Secreted Basement Membrane Molecule SPON-1/F-Spondin in Caenorhabditis elegans Neuronal Migration

Cited by 15 publications

References 65 publications

The Collagens DPY-17 and SQT-3 Direct Anterior–Posterior Migration of the Q Neuroblasts in C. elegans

The Collagens DPY-17 and SQT-3 Direct Anterior–Posterior Migration of the Q Neuroblasts in C. elegans

The Caenorhabditis elegans NF2/Merlin Molecule NFM-1 Nonautonomously Regulates Neuroblast Migration and Interacts Genetically with the Guidance Cue SLT-1/Slit

The Collagens DPY-17 and SQT-3 Direct Anterior-Posterior Migration of the Q Neuroblasts inC. elegans

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