The Difference in the Cytoskeletal Machinery of Growth Cones of Growing Axons and Leading Processes

Miyata, Kaho; Hayashi, Kohei

doi:10.1159/000522200

Cited by 3 publications

(2 citation statements)

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“…Dbn1 over-expression in DRGs and in embryonic cortical neurons results in an increase in axon branches, filopodial protrusions and neurites in vivo and in vitro (Geraldo et al, 2008;Ketschek et al, 2016;Poobalasingam et al, 2022). Additionally, knock down of Dbn1 using RNAi leads to a reduction in filopodia, lamellipodia and axon branching in vitro in several neuronal cell types, including cortical neurons and sensory neurons (Geraldo et al, 2008;Ketschek et al, 2016;Miyata and Hayashi, 2022). To complement these findings and our in vivo results on interstitial axon branching regulators we manipulated layer II/III CNPs in vitro.…”

Section: Dbn1 Over-expression and Loss-of-function Axon Protrusion An...mentioning

confidence: 53%

Drebrin Regulates Collateral Axon Branching in Cortical Layer II/III Somatosensory Neurons

Dorskind,

Sudarsanam,

Hand

et al. 2023

Preprint

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Proper cortical lamination is essential for cognition, learning, and memory. Within the somatosensory cortex, pyramidal excitatory neurons elaborate axon collateral branches in a laminar-specific manner that dictates synaptic partners and overall circuit organization. Here, we leverage mouse models, single-cell labeling and imaging approaches to identify intrinsic regulators of laminar-specific collateral, also termed interstitial, axon branching. We developed new approaches for the robust, sparse, labeling of layer II/III pyramidal neurons to obtain single-cell quantitative assessment of axon branch morphologies. We combined these approaches with cell-autonomous loss-of-function (LOF) and over-expression (OE) manipulations in anin vivocandidate screen to identify regulators of cortical neuron axon branch lamination. We identify a role for the cytoskeletal binding protein drebrin (Dbn1) in regulating layer II/III cortical projection neuron (CPN) collateral axon branchingin vitro.LOF experiments show that Dbn1 is necessary to suppress the elongation of layer II/III CPN collateral axon branches within layer IV, where axon branching by layer II/III CPNs is normally absent. Conversely,Dbn1OE produces excess short axonal protrusions reminiscent of nascent axon collaterals that fail to elongate. Structure-function analyses implicate Dbn1S142phosphorylation and Dbn1 protein domains known to mediate F-actin bundling and microtubule (MT) coupling as necessary for collateral branch initiation upon Dbn1 OE. Taken together, these results contribute to our understanding of the molecular mechanisms that regulate collateral axon branching in excitatory CPNs, a key process in the elaboration of neocortical circuit formation.Significance StatementLaminar-specific axon targeting is essential for cortical circuit formation. Here, we show that the cytoskeletal protein drebrin (Dbn1) regulates excitatory layer II/III cortical projection neuron (CPN) collateral axon branching, lending insight into the molecular mechanisms that underlie neocortical laminar-specific innervation. To identify branching patterns of single cortical neuronsin vivo, we have developed tools that allow us to obtain detailed images of individual CPN morphologies throughout postnatal development and to manipulate gene expression in these same neurons. Our results showing that Dbn1 regulates CPN interstitial axon branching bothin vivoandin vitroand may aid in our understanding of how aberrant cortical neuron morphology contributes to dysfunctions observed in Autism Spectrum Disorder (ASD) and epilepsy.

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Section: Dbn1 Over-expression and Loss-of-function Axon Protrusion An...mentioning

confidence: 53%

Drebrin Regulates Collateral Axon Branching in Cortical Layer II/III Somatosensory Neurons

Dorskind,

Sudarsanam,

Hand

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Moreover, axon elongation is inhibited when the molecular interactions of F-actin and microtubules are disrupted 7,8 , indicating that cytoskeletal regulation in growth cones is essential for axon elongation.Migrating neurons have been observed to form a growth-conelike structure (GCLS) at the tips of the leading process 9 . In vitro experiments have suggested that filopodia and lamellipodia of migrating neurons are similar to those of axonal growth cones, though the molecular mechanisms mediating cytoskeletal remodeling in these GCLSs may be distinct from those operating in axonal growth cones 10 . GCLSs have been implicated in the generation of the traction force required for the migration of cultured cerebellar granule cells 11,12 , suggesting that they may be functionally important mediators of neuronal migration in vivo.…”

mentioning

confidence: 99%

Identification of the growth cone as a probe and driver of neuronal migration in the injured brain

Nakajima,

Sawada,

Umeda

et al. 2024

Nat Commun

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Axonal growth cones mediate axonal guidance and growth regulation. We show that migrating neurons in mice possess a growth cone at the tip of their leading process, similar to that of axons, in terms of the cytoskeletal dynamics and functional responsivity through protein tyrosine phosphatase receptor type sigma (PTPσ). Migrating-neuron growth cones respond to chondroitin sulfate (CS) through PTPσ and collapse, which leads to inhibition of neuronal migration. In the presence of CS, the growth cones can revert to their extended morphology when their leading filopodia interact with heparan sulfate (HS), thus re-enabling neuronal migration. Implantation of an HS-containing biomaterial in the CS-rich injured cortex promotes the extension of the growth cone and improve the migration and regeneration of neurons, thereby enabling functional recovery. Thus, the growth cone of migrating neurons is responsive to extracellular environments and acts as a primary regulator of neuronal migration.

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Drebrin Regulates Collateral Axon Branching in Cortical Layer II/III Somatosensory Neurons

Dorskind,

Sudarsanam,

Hand

et al. 2023

J. Neurosci.

View full text Add to dashboard Cite

Proper cortical lamination is essential for cognition, learning, and memory. Within the somatosensory cortex, pyramidal excitatory neurons elaborate axon collateral branches in a laminar-specific manner that dictates synaptic partners and overall circuit organization. Here, we leverage both male and female mouse models, single-cell labeling and imaging approaches to identify intrinsic regulators of laminar-specific collateral, also termed interstitial, axon branching. We developed new approaches for the robust, sparse, labeling of layer II/III pyramidal neurons to obtain single-cell quantitative assessment of axon branch morphologies. We combined these approaches with cell-autonomous loss-of-function (LOF) and over-expression (OE) manipulations in anin vivocandidate screen to identify regulators of cortical neuron axon branch lamination. We identify a role for the cytoskeletal binding protein drebrin (Dbn1) in regulating layer II/III cortical projection neuron (CPN) collateral axon branchingin vitro.LOF experiments show that Dbn1 is necessary to suppress the elongation of layer II/III CPN collateral axon branches within layer IV, where axon branching by layer II/III CPNs is normally absent. Conversely,Dbn1OE produces excess short axonal protrusions reminiscent of nascent axon collaterals that fail to elongate. Structure-function analyses implicate Dbn1S142phosphorylation and Dbn1 protein domains known to mediate F-actin bundling and microtubule (MT) coupling as necessary for collateral branch initiation onDbn1OE. Taken together, these results contribute to our understanding of the molecular mechanisms that regulate collateral axon branching in excitatory CPNs, a key process in the elaboration of neocortical circuit formation.Significance StatementLaminar-specific axon targeting is essential for cortical circuit formation. Here, we show that the cytoskeletal protein drebrin (Dbn1) regulates excitatory layer II/III cortical projection neuron (CPN) collateral axon branching, lending insight into the molecular mechanisms that underlie neocortical laminar-specific innervation. To identify branching patterns of single cortical neuronsin vivo, we have developed tools that allow us to obtain detailed images of individual CPN morphologies throughout postnatal development and to manipulate gene expression in these same neurons. Our results showing that Dbn1 regulates CPN interstitial axon branching bothin vivoandin vitroand may aid in our understanding of how aberrant cortical neuron morphology contributes to dysfunctions observed in Autism Spectrum Disorder (ASD) and epilepsy.

show abstract

The Difference in the Cytoskeletal Machinery of Growth Cones of Growing Axons and Leading Processes

Cited by 3 publications

References 38 publications

Drebrin Regulates Collateral Axon Branching in Cortical Layer II/III Somatosensory Neurons

Drebrin Regulates Collateral Axon Branching in Cortical Layer II/III Somatosensory Neurons

Identification of the growth cone as a probe and driver of neuronal migration in the injured brain

Drebrin Regulates Collateral Axon Branching in Cortical Layer II/III Somatosensory Neurons

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