Filopodia initiate choices made by sensory neuron growth cones at laminin/fibronectin borders in vitro

Gómez, Timothy M.; Letourneau, Paul C.

doi:10.1523/jneurosci.14-10-05959.1994

Cited by 120 publications

(99 citation statements)

References 96 publications

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“…Integrin-dependent signaling, analogous to that seen in nonneuronal cells, has been reported in a few studies (Gomez and Letourneau, 1994;Gomez et al, 1996;Myers and Gomez, 2011) and mechanochemical signaling through focal adhesion kinase (FAK) has been shown to stabilize the early adhesions (Moore et al, 2009(Moore et al, , 2012Robles and Gomez, 2006).…”

Section: Introductionmentioning

confidence: 91%

Formin-2 regulates stabilization of filopodial tip adhesions in growth cones and affects neuronal outgrowth and pathfinding in vivo

et al. 2015

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Growth cone filopodia are actin-based mechanosensory structures that are essential for chemoreception and the generation of contractile forces necessary for directional motility. However, little is known about the influence of filopodial actin structures on substrate adhesion and filopodial contractility. Formin 2 (Fmn2) localizes along filopodial actin bundles and its depletion does not affect filopodia initiation or elongation. However, Fmn2 activity is required for filopodial tip adhesion maturation and the ability of filopodia to generate traction forces. Dysregulation of filopodia in Fmn2-depleted neurons leads to compromised growth cone motility. Additionally, in mouse fibroblasts, Fmn2 regulates ventral stress fiber assembly and affects the stability of focal adhesions. In the developing chick spinal cord, Fmn2 activity is required cellautonomously for the outgrowth and pathfinding of spinal commissural neurons. Our results reveal an unanticipated function for Fmn2 in neural development. Fmn2 regulates structurally diverse bundled actin structures, parallel filopodial bundles in growth cones and anti-parallel stress fibers in fibroblasts, in turn modulating the stability of substrate adhesions. We propose Fmn2 as a mediator of actin bundle integrity, enabling efficient force transmission to the adhesion sites.

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Section: Introductionmentioning

confidence: 91%

Formin-2 regulates stabilization of filopodial tip adhesions in growth cones and affects neuronal outgrowth and pathfinding in vivo

et al. 2015

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“…These experiments supported a model for growth cone steering based on differential expression of adhesive molecules in the environment. More recently, various in vitro studies have quantified the adhesion of neurites on extracts of purified embryonic substrate-bound adhesion molecules (Gundersen, 1987(Gundersen, , 1988Calof and Lander, 1991;Lamoureux et al, 1992;Lemmon et al, 1992;Gomez and Letourneau, 1994). The majority of these studies showed little correlation between adhesion and neuron outgrowth, indicating that endogenous substrates may not exert their effects on axon guidance principally via relative adhesiveness.…”

Section: Abstract: Neuronal Development; Growth Cones; Filopodia; Gumentioning

confidence: 99%

Filopodial Adhesion Does Not Predict Growth Cone Steering EventsIn Vivo

Isbister

O’Connor

1999

J. Neurosci.

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Migration of growth cones is in part mediated by adhesive interactions between filopodia and the extracellular environment, transmitting forces and signals necessary for pathfinding. To elucidate the role of substrate adhesivity in growth cone pathfinding, we developed an in vivo assay for measuring filopodial-substrate adhesivity using the well-characterized Ti pioneer neuron pathway of the embryonic grasshopper limb. Using time-lapse imaging and a combination of rhodaminephalloidin injections and DiI labeling, we demonstrate that the filopodial retraction rate after treatment with cytochalasin D or elastase reflects the degree of filopodial-substrate adhesivity. Measurements of filopodial retraction rates along regions of known differing substrate adhesivities confirmed the use of this assay to examine filopodial-substrate adhesion during in vivo pathfinding events. We analyzed 359 filopodia from 22 Ti growth cones and found that there is no difference between the retraction rates of filopodia extending toward the correct target (on-axis) and filopodia extending away from the correct target (off-axis). These results indicate on-axis and off-axis filopodia have similar substrate adherence. Interestingly, we observed a 300% increase in the extension rates of on-axis filopodia during Ti growth cone turning events. Therefore, in addition to providing filopodia with important guidance information, regional cues are capable of modulating the filopodial extension rate. The homogeneity in filopodial retraction rates, even among these turning growth cones in which differential adhesivity might be expected to be greatest, strongly establishes that differential adhesion does not govern Ti pioneer neuron migration rate or pathfinding. We propose that the presence of local differences in receptor-mediated second messenger cascades and the resulting assembly of force-generating machinery may underlie the ability of filopodial contacts to regulate growth cone steering in vivo.

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“…These choices are mediated by dynamic sensory structures, lamellipodia and filopodia. Filopodia are particularly important in detecting guidance cues (Gomez and Letourneau, 1994;Kuhn et al, 1994;Dickson, 2002). Signaling by guidance cues can begin within filopodia (Davenport et al, 1993;Robles et al, 2003), and a single filopodial contact is sufficient to turn a growth cone (O'Connor et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor Regulation of Retinal Growth Cone Filopodial Dynamics Is Mediated through Actin Depolymerizing Factor/Cofilin

Gehler¹,

Shaw²,

Sarmiere³

et al. 2004

J. Neurosci.

110

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The molecular mechanisms by which neurotrophins regulate growth cone motility are not well understood. This study investigated the signaling involved in transducing BDNF-induced increases of filopodial dynamics. Our results indicate that BDNF regulates filopodial length and number through a Rho kinase-dependent mechanism. Additionally, actin depolymerizing factor (ADF)/cofilin activity is necessary and sufficient to transduce the effects of BDNF. Our data indicate that activation of ADF/cofilin mimics the effects of BDNF on filopodial dynamics, whereas ADF/cofilin inactivity blocks the effects of BDNF. Furthermore, BDNF promotes the activation of ADF/ cofilin by reducing the phosphorylation of ADF/cofilin. Although inhibition of myosin II also enhances filopodial length, our results indicate that BDNF signaling is independent of myosin II activity and that the two pathways result in additive effects on filopodial length. Thus, filopodial extension is regulated by at least two independent mechanisms. The BDNF-dependent pathway works via regulation of ADF/cofilin, independently of myosin II activity.

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Filopodia initiate choices made by sensory neuron growth cones at laminin/fibronectin borders in vitro

Cited by 120 publications

References 96 publications

Formin-2 regulates stabilization of filopodial tip adhesions in growth cones and affects neuronal outgrowth and pathfinding in vivo

Formin-2 regulates stabilization of filopodial tip adhesions in growth cones and affects neuronal outgrowth and pathfinding in vivo

Filopodial Adhesion Does Not Predict Growth Cone Steering EventsIn Vivo

Brain-Derived Neurotrophic Factor Regulation of Retinal Growth Cone Filopodial Dynamics Is Mediated through Actin Depolymerizing Factor/Cofilin

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