author_facet Carcea, Ioana
Ma'ayan, Avi
Mesias, Roxana
Sepulveda, Bryan
Salton, Stephen R.
Benson, Deanna L.
Carcea, Ioana
Ma'ayan, Avi
Mesias, Roxana
Sepulveda, Bryan
Salton, Stephen R.
Benson, Deanna L.
author Carcea, Ioana
Ma'ayan, Avi
Mesias, Roxana
Sepulveda, Bryan
Salton, Stephen R.
Benson, Deanna L.
spellingShingle Carcea, Ioana
Ma'ayan, Avi
Mesias, Roxana
Sepulveda, Bryan
Salton, Stephen R.
Benson, Deanna L.
The Journal of Neuroscience
Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
General Neuroscience
author_sort carcea, ioana
spelling Carcea, Ioana Ma'ayan, Avi Mesias, Roxana Sepulveda, Bryan Salton, Stephen R. Benson, Deanna L. 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.1821-10.2010 <jats:p>Cortical efferents growing in the same environment diverge early in development. The expression of particular transcription factors dictates the trajectories taken, presumably by regulating responsiveness to guidance cues via cellular mechanisms that are not yet known. Here, we show that cortical neurons that are dissociated and grown in culture maintain their cell type-specific identities defined by the expression of transcription factors. Using this model system, we sought to identify and characterize mechanisms that are recruited to produce cell type-specific responses to Semaphorin 3A (Sema3A), a guidance cue that would be presented similarly to cortical axons<jats:italic>in vivo</jats:italic>. Axons from presumptive corticofugal neurons lacking the transcription factor Satb2 and expressing Ctip2 or Tbr1 respond far more robustly to Sema3A than those from presumptive callosal neurons expressing Satb2. Both populations of axons express similar levels of Sema3A receptors (neuropilin-1, cell adhesion molecule L1, and plexinA4), but significantly, axons from neurons lacking Satb2 internalize more Sema3A, and they do so via a raft-mediated endocytic pathway. We used an<jats:italic>in silico</jats:italic>approach to identify the endocytosis effector flotillin-1 as a Sema3A signaling candidate. We tested the contributions of flotillin-1 to Sema3A endocytosis and signaling, and show that raft-mediated Sema3A endocytosis is defined by and depends on the recruitment of flotillin-1, which mediates LIM domain kinase activation and regulates axon responsiveness to Sema3A in presumptive corticofugal axons.</jats:p> Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A The Journal of Neuroscience
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title Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
title_unstemmed Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
title_full Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
title_fullStr Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
title_full_unstemmed Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
title_short Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
title_sort flotillin-mediated endocytic events dictate cell type-specific responses to semaphorin 3a
topic General Neuroscience
url http://dx.doi.org/10.1523/jneurosci.1821-10.2010
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description <jats:p>Cortical efferents growing in the same environment diverge early in development. The expression of particular transcription factors dictates the trajectories taken, presumably by regulating responsiveness to guidance cues via cellular mechanisms that are not yet known. Here, we show that cortical neurons that are dissociated and grown in culture maintain their cell type-specific identities defined by the expression of transcription factors. Using this model system, we sought to identify and characterize mechanisms that are recruited to produce cell type-specific responses to Semaphorin 3A (Sema3A), a guidance cue that would be presented similarly to cortical axons<jats:italic>in vivo</jats:italic>. Axons from presumptive corticofugal neurons lacking the transcription factor Satb2 and expressing Ctip2 or Tbr1 respond far more robustly to Sema3A than those from presumptive callosal neurons expressing Satb2. Both populations of axons express similar levels of Sema3A receptors (neuropilin-1, cell adhesion molecule L1, and plexinA4), but significantly, axons from neurons lacking Satb2 internalize more Sema3A, and they do so via a raft-mediated endocytic pathway. We used an<jats:italic>in silico</jats:italic>approach to identify the endocytosis effector flotillin-1 as a Sema3A signaling candidate. We tested the contributions of flotillin-1 to Sema3A endocytosis and signaling, and show that raft-mediated Sema3A endocytosis is defined by and depends on the recruitment of flotillin-1, which mediates LIM domain kinase activation and regulates axon responsiveness to Sema3A in presumptive corticofugal axons.</jats:p>
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author Carcea, Ioana, Ma'ayan, Avi, Mesias, Roxana, Sepulveda, Bryan, Salton, Stephen R., Benson, Deanna L.
author_facet Carcea, Ioana, Ma'ayan, Avi, Mesias, Roxana, Sepulveda, Bryan, Salton, Stephen R., Benson, Deanna L., Carcea, Ioana, Ma'ayan, Avi, Mesias, Roxana, Sepulveda, Bryan, Salton, Stephen R., Benson, Deanna L.
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description <jats:p>Cortical efferents growing in the same environment diverge early in development. The expression of particular transcription factors dictates the trajectories taken, presumably by regulating responsiveness to guidance cues via cellular mechanisms that are not yet known. Here, we show that cortical neurons that are dissociated and grown in culture maintain their cell type-specific identities defined by the expression of transcription factors. Using this model system, we sought to identify and characterize mechanisms that are recruited to produce cell type-specific responses to Semaphorin 3A (Sema3A), a guidance cue that would be presented similarly to cortical axons<jats:italic>in vivo</jats:italic>. Axons from presumptive corticofugal neurons lacking the transcription factor Satb2 and expressing Ctip2 or Tbr1 respond far more robustly to Sema3A than those from presumptive callosal neurons expressing Satb2. Both populations of axons express similar levels of Sema3A receptors (neuropilin-1, cell adhesion molecule L1, and plexinA4), but significantly, axons from neurons lacking Satb2 internalize more Sema3A, and they do so via a raft-mediated endocytic pathway. We used an<jats:italic>in silico</jats:italic>approach to identify the endocytosis effector flotillin-1 as a Sema3A signaling candidate. We tested the contributions of flotillin-1 to Sema3A endocytosis and signaling, and show that raft-mediated Sema3A endocytosis is defined by and depends on the recruitment of flotillin-1, which mediates LIM domain kinase activation and regulates axon responsiveness to Sema3A in presumptive corticofugal axons.</jats:p>
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spelling Carcea, Ioana Ma'ayan, Avi Mesias, Roxana Sepulveda, Bryan Salton, Stephen R. Benson, Deanna L. 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.1821-10.2010 <jats:p>Cortical efferents growing in the same environment diverge early in development. The expression of particular transcription factors dictates the trajectories taken, presumably by regulating responsiveness to guidance cues via cellular mechanisms that are not yet known. Here, we show that cortical neurons that are dissociated and grown in culture maintain their cell type-specific identities defined by the expression of transcription factors. Using this model system, we sought to identify and characterize mechanisms that are recruited to produce cell type-specific responses to Semaphorin 3A (Sema3A), a guidance cue that would be presented similarly to cortical axons<jats:italic>in vivo</jats:italic>. Axons from presumptive corticofugal neurons lacking the transcription factor Satb2 and expressing Ctip2 or Tbr1 respond far more robustly to Sema3A than those from presumptive callosal neurons expressing Satb2. Both populations of axons express similar levels of Sema3A receptors (neuropilin-1, cell adhesion molecule L1, and plexinA4), but significantly, axons from neurons lacking Satb2 internalize more Sema3A, and they do so via a raft-mediated endocytic pathway. We used an<jats:italic>in silico</jats:italic>approach to identify the endocytosis effector flotillin-1 as a Sema3A signaling candidate. We tested the contributions of flotillin-1 to Sema3A endocytosis and signaling, and show that raft-mediated Sema3A endocytosis is defined by and depends on the recruitment of flotillin-1, which mediates LIM domain kinase activation and regulates axon responsiveness to Sema3A in presumptive corticofugal axons.</jats:p> Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A The Journal of Neuroscience
spellingShingle Carcea, Ioana, Ma'ayan, Avi, Mesias, Roxana, Sepulveda, Bryan, Salton, Stephen R., Benson, Deanna L., The Journal of Neuroscience, Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A, General Neuroscience
title Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
title_full Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
title_fullStr Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
title_full_unstemmed Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
title_short Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
title_sort flotillin-mediated endocytic events dictate cell type-specific responses to semaphorin 3a
title_unstemmed Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A
topic General Neuroscience
url http://dx.doi.org/10.1523/jneurosci.1821-10.2010