Dynamics of target recognition by interstitial axon branching along developing cortical axons

Bastmeyer, Martin; O’Leary, D. D. M.

doi:10.1523/jneurosci.16-04-01450.1996

Cited by 111 publications

(108 citation statements)

References 27 publications

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“…The results of this study suggest that mechanical parameters have profound effects on neuronal morphology, specifically branching, and may be one of the cues that neurons integrate when making critical pathfinding decisions. Furthermore, the fact that neurons can respond to substrate deformability by altering branch formation may have important implications for design of appropriate matrices for neuronal regeneration [30,31] and for formulating models that describe how branching occurs during development [16,21]. Spinal cord neurons on soft substrates.…”

Section: Resultsmentioning

confidence: 99%

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Neurite branching on deformable substrates

et al. 2002

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The mechanical properties of substrates underlying cells can have profound effects on cell structure and function. To examine the effect of substrate deformability on neuronal cell growth, proteinlaminated polyacrylamide gels were prepared with differing amounts of bisacrylamide to generate substrates of varying deformability with elastic moduli ranging from 500 to 5500 dyne/cm 2 . Mouse spinal cord primary neuronal cells were plated on the gels and allowed to grow and extend neurites for several weeks in culture. While neurons grew well on the gels, glia, which are normally cocultured with the neurons, did not survive on these deformable substrates even though the chemical environment was permissive for their growth. Substrate flexibility also had a significant effect on neurite branching. Neurons grown on softer substrates formed more than three times as many branches as those grown on stiffer gels. These results show that mechanical properties of the substrate specifically direct the formation of neurite branches, which are critical for appropriate synaptic connections during development and regeneration.

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Section: Resultsmentioning

confidence: 99%

“…Developmental biology studies have highlighted the importance of branch formation during establishment of connections in the nervous system [21][22][23][24]. Further research on axonal extension has shown that the primary growth cone is responsible for delineating future branch points along the axon [25].…”

Section: Discussionmentioning

confidence: 99%

Neurite branching on deformable substrates

et al. 2002

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“…New axon branches emerge as F-actin-rich filopodia (Bastmeyer and O'Leary, 1996), which evolve into growth cones after microtubule invasion (Dent and Kalil, 2001) (for review, see Luo, 2002).…”

Section: Integrin-mediated Adhesion Promotes Increased Neurite Branchmentioning

confidence: 99%

“…Genetic studies in Drosophila indicate that Abl regulates axon guidance through interactions with F-actin and microtubules (Wills et al, 1999a). Splaying of microtubule bundles at axon branch sites is followed by localized actin polymerization and the emergence of an F-actin-rich protrusion that evolves into a new growth cone (Bastmeyer and O'Leary, 1996;Dent et al, 1999;Dent and Kalil, 2001). In fibroblasts, Arg requires F-actin-and microtubule-binding domains located in its C-terminal half to promote adhesion-dependent protrusions at the periphery Miller et al, 2004).…”

Section: Possible Downstream Targets Of Abl and Arg In Regulation Of mentioning

confidence: 99%

Integrin-Mediated Dendrite Branch Maintenance Requires Abelson (Abl) Family Kinases

Moresco¹,

Donaldson²,

Williamson³

et al. 2005

J. Neurosci.

134

133

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Dendrite arbor structure is a critical determinant of nervous system function that must be actively maintained throughout life, but the signaling pathways that regulate dendrite maintenance are essentially unknown. We report that the Abelson (Abl) and Abl-related gene (Arg) nonreceptor tyrosine kinases are required for maintenance of cortical dendrites in the mouse brain. arg Ϫ/Ϫ cortical dendrites initially develop normally and are indistinguishable from wild-type dendrites at postnatal day 21. Dendrite branches are not efficiently maintained in arg Ϫ/Ϫ neurons, leading to a reduction in dendrite arbor size by early adulthood. More severe dendrite loss is observed in abl Ϫ/Ϫ arg Ϫ/Ϫ neurons. Elevation of Arg kinase activity in primary cortical neurons promotes axon and dendrite branching. Activation of integrin receptors by adhesion to laminin-1 or Semaphorin 7A also promotes neurite branching in cortical neurons, but this response is absent in arg Ϫ/Ϫ neurons because of the reduced dynamic behavior of mutant neurite branches. These data suggest that integrin signaling through Abl and Arg support cortical dendrite branch maintenance by promoting dendrite branch dynamics in response to adhesive cues.

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“…In vivo (Bastmeyer and O'Leary, 1996;Portera-Cailliau et al, 2005;Meyer and Smith, 2006) and in vitro (Ruthel and Hollenbeck, 2000;Dent et al, 2004), the outgrowth of axons and the extension of branches are independently regulated such that branches can extend while their axons stall or retract (Luo and O'Leary, 2005). However, the mechanisms whereby axons and their branches can have differential rates of outgrowth are unknown.…”

Section: Introductionmentioning

confidence: 99%

Differential Outgrowth of Axons and their Branches Is Regulated by Localized Calcium Transients

Hutchins¹,

Kalil²

2008

J. Neurosci.

110

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During development axon outgrowth and branching are independently regulated such that axons can stall or retract while their interstitial branches extend toward targets. Previous studies have shown that guidance cues and intracellular signaling components can promote branching of cortical axons without affecting axon outgrowth. However, the mechanisms that regulate differential outgrowth of axons and their branches are not well understood. Based on our previous work showing the importance of localized repetitive calcium transients in netrin-1-induced cortical axon branching, we sought to investigate the role of calcium signaling in regulating differential outgrowth of axons and their branches. Using fluorescence calcium imaging of dissociated developing cortical neurons, we show that localized spontaneous calcium transients of different frequencies occur in restricted regions of axons and their branches. Higher frequencies occur in more rapidly extending processes whereas lower frequencies occur in processes that stall or retract. Direct induction of localized calcium transients with photolysis of caged calcium induced rapid outgrowth of axonal processes. Surprisingly outgrowth of one axonal process was almost invariably accompanied by simultaneous retraction of another process belonging to the same axon, suggesting a competitive mechanism for differential process outgrowth. Conversely, reducing frequencies of calcium transients with nifedipine and TTX reduced the incidence of differential process outgrowth. Together these results suggest a novel activity-dependent mechanism whereby intrinsic localized calcium transients regulate the competitive growth of axons and their branches. These mechanisms may also be important for the development of cortical connectivity in vivo.

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Dynamics of target recognition by interstitial axon branching along developing cortical axons

Cited by 111 publications

References 27 publications

Neurite branching on deformable substrates

Neurite branching on deformable substrates

Integrin-Mediated Dendrite Branch Maintenance Requires Abelson (Abl) Family Kinases

Differential Outgrowth of Axons and their Branches Is Regulated by Localized Calcium Transients

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