Pontocerebellar Axon Guidance: Neuropilin-1- and Semaphorin 3A-Sensitivity Gradients across Basilar Pontine Nuclei and Semaphorin 3A Variation across Cerebellum

Solowska, Joanna M.; Mazurek, Agnieszka; Weinberger, Lauren; Baird, Douglas H.

doi:10.1006/mcne.2002.1187

Cited by 24 publications

(20 citation statements)

References 45 publications

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“…Together, the precise mechanisms of how VEGF controls neuron migration are still ill defined. Since GCs do not express Npn-1 in vivo (Solowska et al, 2002; this study), the VEGF isoforms must regulate GC migration via a distinct mechanism in the cerebellum. Also, contrary to the effects of VEGF on motoneuron migration, GCs and their growth cones were chemoattracted by VEGF in vitro and ex vivo, implying distinct mechanisms of GC migration.…”

Section: Discussionmentioning

confidence: 86%

Matrix-Binding Vascular Endothelial Growth Factor (VEGF) Isoforms Guide Granule Cell Migration in the Cerebellum via VEGF Receptor Flk1

et al. 2010

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Vascular endothelial growth factor (VEGF) regulates angiogenesis, but also has important, yet poorly characterized roles in neuronal wiring. Using several genetic and in vitro approaches, we discovered a novel role for VEGF in the control of cerebellar granule cell (GC) migration from the external granule cell layer (EGL) toward the Purkinje cell layer (PCL). GCs express the VEGF receptor Flk1, and are chemoattracted by VEGF, whose levels are higher in the PCL than EGL. Lowering VEGF levels in mice in vivo or ectopic VEGF expression in the EGL ex vivo perturbs GC migration. Using GC-specific Flk1 knock-out mice, we provide for the first time in vivo evidence for a direct chemoattractive effect of VEGF on neurons via Flk1 signaling. Finally, using knock-in mice expressing single VEGF isoforms, we show that pericellular deposition of matrix-bound VEGF isoforms around PC dendrites is necessary for proper GC migration in vivo. These findings identify a previously unknown role for VEGF in neuronal migration.

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Section: Discussionmentioning

confidence: 86%

Matrix-Binding Vascular Endothelial Growth Factor (VEGF) Isoforms Guide Granule Cell Migration in the Cerebellum via VEGF Receptor Flk1

et al. 2010

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“…Mouse brains at various stages of development were sectioned on a cryostat and prepared for single-label visualization of P60-katanin or P80-katanin immunoreactivity using a standard peroxidase technique (Solowska et al, 2002;Karabay et al, 2004). Brains from at least three mice at each stage were serially sectioned and immunolabeled.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Microtubule Severing by Katanin Subunits during Neuronal Development

Solowska²,

Qiang³

et al. 2005

Journal of Neuroscience

101

130

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Katanin, the microtubule-severing protein, consists of a subunit termed P60 that breaks the lattice of the microtubule and another subunit termed P80, the functions of which are not well understood. Data presented here show that the ratio of P60 to P80 varies markedly in different tissues, at different phases of development, and regionally within the neuron. P80 is more concentrated in the cell body and less variable during development, whereas P60 often shows concentrations in the distal tips of processes as well as dramatic spikes in expression at certain developmental stages. Overexpression of P60 at various stages in the differentiation of cultured hippocampal neurons results in substantial loss of microtubule mass and a diminution in total process length. In comparison, overexpression of P80, which is thought to augment the severing of microtubules by P60, results in a milder loss of microtubule mass and diminution in process length. At the developmental stage corresponding to axogenesis, overexpression of P60 decreases the total number of processes extended by the neuron, whereas overexpression of P80 produces the opposite result, suggesting that the effects on neuronal morphology are dependent on the degree of microtubule severing and loss of polymer. The microtubules that occupy the axon are notably more resistant to depolymerization in response to excess P60 or P80 than microtubules elsewhere in the neuron, suggesting that regional differences in the susceptibility of microtubules to severing proteins may be a critical factor in the generation and maintenance of neuronal polarity.

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“…Sections of mouse brain at various stages of development were obtained from a cryostat and prepared for single-label visualization of P60-katanin immunoreactivity using a standard peroxidase technique (Solowska et al, 2002). Brains from at least three mice at each stage were completely sectioned and immunolabeled.…”

Section: P60-katanin Sequencing and Preparation Of Probesmentioning

confidence: 99%

“…For explants of basilar pontine neurons, the basilar pontine nuclei (BPN) were removed by excising the superficial swellings just caudal to the cephalic flexure. Microexplants ϳ200 -300 m in diameter were dissected from the BPN and cultured as a source of axons that develop in situ as mossy fibers (Hatten et al, 1998;Solowska et al, 2002). Reaggregates of cerebellar cells were prepared as target cells for BPN axons.…”

Section: P60-katanin Sequencing and Preparation Of Probesmentioning

confidence: 99%

Axonal Growth Is Sensitive to the Levels of Katanin, a Protein That Severs Microtubules

Karabay

Yu²,

Solowska³

et al. 2004

J. Neurosci.

140

139

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Katanin is a heterodimeric enzyme that severs microtubules from the centrosome so that they can move into the axon. Katanin is broadly distributed in the neuron, and therefore presumably also severs microtubules elsewhere. Such severing would generate multiple short microtubules from longer microtubules, resulting in more microtubule ends available for assembly and interaction with other structures. In addition, shorter microtubules are thought to move more rapidly and undergo organizational changes more readily than longer microtubules. In dividing cells, the levels of P60-katanin (the subunit with severing properties) increase as the cell transitions from interphase to mitosis. This suggests that katanin is regulated in part by its absolute levels, given that katanin activity is high during mitosis. In the rodent brain, neurons vary significantly in katanin levels, depending on their developmental stage. Levels are high during rapid phases of axonal growth but diminish as axons reach their targets. Similarly, in neuronal cultures, katanin levels are high when axons are allowed to grow avidly but drop when the axons are presented with target cells that cause them to stop growing. Expression of a dominant-negative P60-katanin construct in cultured neurons inhibits microtubule severing and is deleterious to axonal growth. Overexpression of wild-type P60-katanin results in excess microtubule severing and is also deleterious to axonal growth, but this only occurs in some neurons. Other neurons are relatively unaffected by overexpression. Collectively, these observations indicate that axonal growth is sensitive to the levels of P60-katanin, but that other factors contribute to modulating this sensitivity.

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Pontocerebellar Axon Guidance: Neuropilin-1- and Semaphorin 3A-Sensitivity Gradients across Basilar Pontine Nuclei and Semaphorin 3A Variation across Cerebellum

Cited by 24 publications

References 45 publications

Matrix-Binding Vascular Endothelial Growth Factor (VEGF) Isoforms Guide Granule Cell Migration in the Cerebellum via VEGF Receptor Flk1

Matrix-Binding Vascular Endothelial Growth Factor (VEGF) Isoforms Guide Granule Cell Migration in the Cerebellum via VEGF Receptor Flk1

Regulation of Microtubule Severing by Katanin Subunits during Neuronal Development

Axonal Growth Is Sensitive to the Levels of Katanin, a Protein That Severs Microtubules

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