Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin Mutants

Newquist, Gunnar; Drennan, J. M.; Lamanuzzi, Matthew; Walker, Kirsti; Clemens, James C.; Kidd, Thomas

doi:10.1016/j.celrep.2013.02.017

Cited by 19 publications

(26 citation statements)

References 65 publications

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“…In genetically mosaic animals where fra is removed specifically from R8s, ~90% fail to reach the M3 layer (Timofeev et al, 2012). In contrast, the failure rate in whole animal Net mutants ( NetA and NetB double mutant, referred to as Net null in the main text) (Newquist et al, 2013) is ~50% (Timofeev et al, 2012). These data raise the possibility of a second Fra ligand acting in parallel with Net .…”

Section: Resultsmentioning

confidence: 97%

Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system

Akin

Zipursky

2016

eLife

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Axon guidance is proposed to act through a combination of long- and short-range attractive and repulsive cues. The ligand-receptor pair, Netrin (Net) and Frazzled (Fra) (DCC, Deleted in Colorectal Cancer, in vertebrates), is recognized as the prototypical effector of chemoattraction, with roles in both long- and short-range guidance. In the Drosophila visual system, R8 photoreceptor growth cones were shown to require Net-Fra to reach their target, the peak of a Net gradient. Using live imaging, we show, however, that R8 growth cones reach and recognize their target without Net, Fra, or Trim9, a conserved binding partner of Fra, but do not remain attached to it. Thus, despite the graded ligand distribution along the guidance path, Net-Fra is not used for chemoattraction. Based on findings in other systems, we propose that adhesion to substrate-bound Net underlies both long- and short-range Net-Fra-dependent guidance in vivo, thereby eroding the distinction between them.DOI: http://dx.doi.org/10.7554/eLife.20762.001

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Section: Resultsmentioning

confidence: 97%

Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system

Akin

Zipursky

2016

eLife

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“…gcm-Gal4,tubGal80 ts (Soustelle et al, 2007). The other strains used were gcm 6Kb> 42; fra 3 (von Hilchen et al, 2010); UAS-fra (von Hilchen et al, 2010); UAS-fra-RNAi (Manhire-Heath et al, 2013); UAS-fra Δ C (Garbe et al, 2007); gcm rA87 (Vincent et al, 1996); gcm N7-4 (Vincent et al, 1996); UAS-gcm (F18A ) (Bernardoni et al, 1998); UAS-gcm-RNAi; gcm> GFP /gcm> GFP (used as a homozygous mutant of gcm ) (Popkova et al, 2012); UAS-string (Inaba et al, 2011); UAS-dacapo (Lane et al, 1996); gcm 34 (Vincent et al, 1996); NetA Δ (von Hilchen et al, 2010; Newquist et al, 2013a, 2013b); NetB Δ (von Hilchen et al, 2010; Newquist et al, 2013a, 2013b); NetA Δ NetB TM (Brankatschk and Dickson, 2006); NetA Δ NetB myc Brankatschk and Dickson, 2006) (note that both NetA Δ NetB TM and NetA Δ NetB myc encode the c-myc epitope tags); UAS-NetB-RNAi ( Manhire-Heath et al, 2013 ); UAS-NetB (Timofeev et al, 2012); NP4151-Gal4 and NP4012-Gal4 (DGRC, Kyoto) (Timofeev et al, 2012; Hayashi et al, 2002); UAS-NetA-RNAi (Manhire-Heath et al, 2013); UAS-NetA (Newquist et al, 2013a , 2013b); unc5 8 (Labrador et al, 2005); collagen-Gal4 (Asha et al, 2003); engrailed-Gal4 driver (Hidalgo, 1994; Lawrence and Morata, 1976); GMR 29F05-Gal4 (Pfeiffer et al, 2008); UAS-unc5-RNAi; UAS-unc5 (von Hilchen et al, 2010); nsyb-Gal4>GFP-LAMP (B# 42714); elav-Gal4 . The RNAi lines were obtained from Bloomington and/or the VDRC stock center.…”

Section: Materials and Methodsmentioning

confidence: 99%

The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled

Gupta

Kumar

Cattenoz

et al. 2016

eLife

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Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination.DOI: http://dx.doi.org/10.7554/eLife.15983.001

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“…We have developed a fly line that lacks both Drosophila Netrin genes, NetA and NetB , that survives to adulthood and can be maintained as homozygotes [22]. In the course of characterizing the adult phenotypes of NetAB flies, we eliminated a role for a NetB intronic gene, hog , in the NetAB mutant phenotype.…”

Section: Introductionmentioning

confidence: 99%

Control of Male and Female Fertility by the Netrin Axon Guidance Genes

et al. 2013

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The netrin axon guidance genes have previously been implicated in fertility in C. elegans and in vertebrates. Here we show that adult Drosophila lacking both netrin genes, NetA and NetB, have fertility defects in both sexes together with an inability to fly and reduced viability. NetAB females produce fertilized eggs at a much lower rate than wild type. Oocyte development and ovarian innervation are unaffected in NetAB females, and the reproductive tract appears normal. A small gene, hog, that resides in an intron of NetB does not contribute to the NetAB phenotype. Restoring endogenous NetB expression rescues egg-laying, but additional genetic manipulations, such as restoration of netrin midline expression and inhibition of cell death have no effect on fertility. NetAB males induce reduced egg-laying in wild type females and display mirror movements of their wings during courtship. Measurement of courtship parameters revealed no difference compared to wild type males. Transgenic manipulations failed to rescue male fertility and mirror movements. Additional genetic manipulations, such as removal of the enabled gene, a known suppressor of the NetAB embryonic CNS phenotype, did not improve the behavioral defects. The ability to fly was rescued by inhibition of neuronal cell death and pan-neural NetA expression. Based on our results we hypothesize that the adult fertility defects of NetAB mutants are due to ovulation defects in females and a failure to properly transfer sperm proteins in males, and are likely to involve multiple neural circuits.

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Blocking Apoptotic Signaling Rescues Axon Guidance in Netrin Mutants

Cited by 19 publications

References 65 publications

Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system

Frazzled promotes growth cone attachment at the source of a Netrin gradient in the Drosophila visual system

The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled

Control of Male and Female Fertility by the Netrin Axon Guidance Genes

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