Genetics of cell and axon migrations in <i>Caenorhabditis elegans</i>

Hedgecock, Edward M.; Culotti, Joseph G.; Hall, David H.; Stern, Brian D.

doi:10.1242/dev.100.3.365

Cited by 305 publications

(23 citation statements)

References 23 publications

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“…The dorsal ectopic synapses in the VD neurons of unc-30 mutant animals (not observed in lin-14 ) are in turn recapitulated in animals lacking the unc-55 orphan nuclear receptor, in which VD MNs form aberrant synapses in the dorsal cord, as previously shown ( Extended Data Fig. 2b ; schematized in Fig.1e , f ) 6 , 7 , while DD wiring at the L1 stage is normal. Taken together, the unc-30 phenotype in the DD and VD neurons can be viewed as a “composite” of the two individual phenotypes of lin-14 (DD neurons at L1 stage) and unc-55 (VD neurons at later stages) ( Fig.1e , f schematic).…”

supporting

confidence: 78%

Spatiotemporal control of a novel synaptic organizer molecule

Howell

White

Hobert

2015

Nature

104

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Synapse formation is a process tightly controlled in space and time. How gene regulatory mechanisms specify spatial and temporal aspects of synapse formation is not well understood. In the nematode Caenorhabditis elegans, two subtypes of the D-type inhibitory motor neuron (MN) classes, the dorsal D (DD) and ventral D (VD) neurons, extend axons along both the dorsal and ventral nerve cords. The embryonically generated DD motor neurons initially innervate ventral muscles in the first (L1) larval stage and receive their synaptic input from cholinergic motor neurons in the dorsal cord. They rewire by the end of the L1 moult to innervate dorsal muscles and to be innervated by newly formed ventral cholinergic motor neurons. VD motor neurons develop after the L1 moult; they take over the innervation of ventral muscles and receive their synaptic input from dorsal cholinergic motor neurons. We show here that the spatiotemporal control of synaptic wiring of the D-type neurons is controlled by an intersectional transcriptional strategy in which the UNC-30 Pitx-type homeodomain transcription factor acts together, in embryonic and early larval stages, with the temporally controlled LIN-14 transcription factor to prevent premature synapse rewiring of the DD motor neurons and, together with the UNC-55 nuclear hormone receptor, to prevent aberrant VD synaptic wiring in later larval and adult stages. A key effector of this intersectional transcription factor combination is a novel synaptic organizer molecule, the single immunoglobulin domain protein OIG-1. OIG-1 is perisynaptically localized along the synaptic outputs of the D-type motor neurons in a temporally controlled manner and is required for appropriate selection of both pre- and post-synaptic partners.

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supporting

confidence: 78%

Spatiotemporal control of a novel synaptic organizer molecule

Howell

White

Hobert

2015

Nature

104

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“…Collapsin response mediator proteins (CRMPs) are a family of cytosolic proteins whose expression patterns are developmentally regulated within the nervous system ( , ). These proteins are assumed to mediate intracellular responses to collapsin through a signal transduction cascade involving G protein () and have significant homology with the product of unc -33 in Caenorhabditis elegans , mutation of which results in abnormal outgrowth of axons, leading to severe incoordination ( − ).…”

mentioning

confidence: 99%

Neurofibrillary Tangle-Associated Collapsin Response Mediator Protein-2 (CRMP-2) Is Highly Phosphorylated on Thr-509, Ser-518, and Ser-522

2000

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3F4, a monoclonal antibody raised against partially purified paired helical filaments (PHFs), strongly labeled neurofibrillary tangles and some plaque neurites but barely labeled neuropil threads. The levels of the 65-kDa antigen were significantly increased in the soluble fraction of the brains affected by Alzheimer's disease (AD), as compared with that in the case of control brains. The antigen was previously identified as human collapsin response mediator protein-2 (hCRMP-2) by sequencing the immunoaffinity-purified 65-kDa antigen [Yoshida, H., Watanabe, A., and Ihara, Y. (1998) J. Biol. Chem. 273, 9761-9768]. Here, we show that the 3F4 antigen represents a highly phosphorylated form of CRMP-2. The 3F4-reactive phosphoepitope was localized to the carboxyl-terminal portion of hCRMP-2, and was created by a novel 45-50-kDa protein kinase in rat brain extract. Site-directed mutagenesis of this portion showed that multiple sites of CRMP-2 are differentially phosphorylated within residues 507-522, and that phosphorylation of three sites, Thr-509, Ser-518, and Ser-522, is required for full 3F4 binding. The phosphorylation of this particular portion carboxyl-terminal to the basic region of CRMP-2 may play an important role in regulating its activity, and may be involved in the formation of degenerating neurites in AD brain.

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“…Many different processes in C. elegans development are regulated by Wnt signaling, here we will focus on neuronal migrations along the anteroposterior axis, Chapter 1 either during embryogenesis or larval development. During embryogenesis, the bilateral pairs of neurons CAN, HSN, BDU, and ALM, migrate to distinct positions (Hedgecock et al, 1987;Sulston, 1983) (Fig. 3A).…”

Section: Elegans As a Model To Study Cell Migrationmentioning

confidence: 99%

“…2B). During embryogenesis, four bilateral pairs of neurons migrate along the developing anteroposterior body axis (Hedgecock et al, 1987;Sulston, 1983). Two neurons migrate posteriorly: de canal-associated neurons (CANs) migrate from the head to the mid-body region, while the anterior lateral microtubule neurons (ALMs) migrate from a position close to the epidermal seam cell V1 to seam cell V3.…”

Section: The Crd Constitutes Most Of Cam-1's Functionmentioning

confidence: 99%

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Regulation of Wnt signal transduction

Veen¹

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Wnt signaling is essential during embryonic development and adult tissue homeostasis, controlling processes as diverse as cell proliferation, cell migration and differentiation.Wnt ligands can trigger different canonical or non-canonical signaling pathways depending on the receptors that are present on responding cells. One of these receptors is Ror, an evolutionarily conserved receptor tyrosine kinase with important functions in development and cancer. Key functions of Ror signaling are in cell migration and cell polarity, where it acts as a direct signaling receptor to control these processes. Studies in the nematodeCaenorhabditis elegans have shown, however, that it can also act indirectly by sequestering Wnt ligands away from responding cells. Although Ror signaling is considered a non-canonical Wnt signaling pathway, research in the past years has provided insight in the extensive cross-talk with other Wnt pathways, including the canonical Wnt/b-catenin signaling pathway. Here, we review what is currently known about Ror in vertebrate and Caenorhabditis elegans (C. elegans) development. Moreover, we discuss how insight into the cell non-autonomous function of Ror in C.elegans could further our understanding of the role of Ror in cancer.

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Genetics of cell and axon migrations in Caenorhabditis elegans

Cited by 305 publications

References 23 publications

Spatiotemporal control of a novel synaptic organizer molecule

Spatiotemporal control of a novel synaptic organizer molecule

Neurofibrillary Tangle-Associated Collapsin Response Mediator Protein-2 (CRMP-2) Is Highly Phosphorylated on Thr-509, Ser-518, and Ser-522

Regulation of Wnt signal transduction

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