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Semaphorin signaling in vertebrate neural circuit assembly.

Yoshida Y - Front Mol Neurosci (2012)

Bottom Line: The major semaphorin receptors are plexins and neuropilins, however other receptors and co-receptors also mediate signaling by semaphorins.Upon semaphorin binding to their receptors, downstream signaling molecules transduce this event within cells to mediate further events, including alteration of microtubule and actin cytoskeletal dynamics.Here, I review recent studies on semaphorin signaling in vertebrate neural circuit assembly, with the goal of highlighting how this diverse family of cues and receptors imparts exquisite specificity to neural complex connectivity.

View Article: PubMed Central - PubMed

Affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center Cincinnati, OH, USA.

ABSTRACT
Neural circuit formation requires the coordination of many complex developmental processes. First, neurons project axons over long distances to find their final targets and then establish appropriate connectivity essential for the formation of neuronal circuitry. Growth cones, the leading edges of axons, navigate by interacting with a variety of attractive and repulsive axon guidance cues along their trajectories and at final target regions. In addition to guidance of axons, neuronal polarization, neuronal migration, and dendrite development must be precisely regulated during development to establish proper neural circuitry. Semaphorins consist of a large protein family, which includes secreted and cell surface proteins, and they play important roles in many steps of neural circuit formation. The major semaphorin receptors are plexins and neuropilins, however other receptors and co-receptors also mediate signaling by semaphorins. Upon semaphorin binding to their receptors, downstream signaling molecules transduce this event within cells to mediate further events, including alteration of microtubule and actin cytoskeletal dynamics. Here, I review recent studies on semaphorin signaling in vertebrate neural circuit assembly, with the goal of highlighting how this diverse family of cues and receptors imparts exquisite specificity to neural complex connectivity.

No MeSH data available.


Sema3E-PlexD1 signaling regulates pathway-specific synapse formation in the striatum. Direct and indirect pathway MSNs are functionally and molecularly distinct. Direct pathway MSNs express type 1 dopamine receptors (Drd1) and indirect pathway MSNs express type 2 dopamine receptors (Drd2). PlexD1 is exprsssed by Drd1on-direct pathway MSNs in the striatum, whereas Sema3E is expressed by subsets of neurons in the main thalamic nuclei that project to the striatum. Loss of Sema3E-PlexD1 signaling causes functional and anatomical rearrangement of thalamostriatal synapses specifically in direct pathway MSNs without effects on corticostriatal synapses.
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Figure 5: Sema3E-PlexD1 signaling regulates pathway-specific synapse formation in the striatum. Direct and indirect pathway MSNs are functionally and molecularly distinct. Direct pathway MSNs express type 1 dopamine receptors (Drd1) and indirect pathway MSNs express type 2 dopamine receptors (Drd2). PlexD1 is exprsssed by Drd1on-direct pathway MSNs in the striatum, whereas Sema3E is expressed by subsets of neurons in the main thalamic nuclei that project to the striatum. Loss of Sema3E-PlexD1 signaling causes functional and anatomical rearrangement of thalamostriatal synapses specifically in direct pathway MSNs without effects on corticostriatal synapses.

Mentions: The striatum receives convergent excitatory inputs from the cortex and thalamus. Specific excitatory synaptic connections are formed between axons arising from these two regions and their two functionally distinct populations of targets: the direct and the indirect pathway of striatal medium spiny neurons (MSNs; Surmeier et al., 2007). Very recently, Ding et al. (2012) demonstrated that Sema3E-PlexD1 signaling controls pathway-specific synapse formation in the striatum. The authors first find that PlexD1 is expressed by the direct pathway, but not the indirect pathway, MSNs, whereas Sema3E is expressed in the thalamus and in deep cortical layers, the two principal sources of glutamatergic inputs to the striatum (Ding et al., 2012). AMPA receptor-mediated spontaneous miniature excitatory postsynaptic currents (mEPSCs) were measured using the whole-cell voltage-clamp recording, and loss of either Sema3E or PlexD1 was found to lead to a large increase in mEPSC frequency, but not amplitude, in direct pathway MSNs (Ding et al., 2012). Furthermore, optogenetic activation of thalamostriatal axons showed that loss of PlexD1 or Sema3E leads to large evoked thalamostriatal EPSCs in the direct pathway MSNs, and loss of PlexD1 increases thalamostriatal synapse number (Ding et al., 2012). In thalamostriatal projections, Sema3E is secreted by axons and PlexD1 is expressed by postsynaptic neurons. Therefore, it is unlikely that Sema3E-PlexD1 signaling affects the targeting axons, as is observed in the spinal cord (Pecho-Vrieseling et al., 2009). Instead, Sema3E-PlexD1 signaling may control thalamostriatal synaptic strength by regulating postsynaptic sites through the PlexD1 receptor (Figure 5). For example, PlexD1 receptor signaling may alter the cytoskeleton or regulate glutamate receptor trafficking and stabilization. Alternatively, Sema3E-PlexD1 signaling may produce a secreted molecule to induce a retrograde signal in the postsynaptic sites that repels thalamostriatal axons.


Semaphorin signaling in vertebrate neural circuit assembly.

Yoshida Y - Front Mol Neurosci (2012)

Sema3E-PlexD1 signaling regulates pathway-specific synapse formation in the striatum. Direct and indirect pathway MSNs are functionally and molecularly distinct. Direct pathway MSNs express type 1 dopamine receptors (Drd1) and indirect pathway MSNs express type 2 dopamine receptors (Drd2). PlexD1 is exprsssed by Drd1on-direct pathway MSNs in the striatum, whereas Sema3E is expressed by subsets of neurons in the main thalamic nuclei that project to the striatum. Loss of Sema3E-PlexD1 signaling causes functional and anatomical rearrangement of thalamostriatal synapses specifically in direct pathway MSNs without effects on corticostriatal synapses.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368236&req=5

Figure 5: Sema3E-PlexD1 signaling regulates pathway-specific synapse formation in the striatum. Direct and indirect pathway MSNs are functionally and molecularly distinct. Direct pathway MSNs express type 1 dopamine receptors (Drd1) and indirect pathway MSNs express type 2 dopamine receptors (Drd2). PlexD1 is exprsssed by Drd1on-direct pathway MSNs in the striatum, whereas Sema3E is expressed by subsets of neurons in the main thalamic nuclei that project to the striatum. Loss of Sema3E-PlexD1 signaling causes functional and anatomical rearrangement of thalamostriatal synapses specifically in direct pathway MSNs without effects on corticostriatal synapses.
Mentions: The striatum receives convergent excitatory inputs from the cortex and thalamus. Specific excitatory synaptic connections are formed between axons arising from these two regions and their two functionally distinct populations of targets: the direct and the indirect pathway of striatal medium spiny neurons (MSNs; Surmeier et al., 2007). Very recently, Ding et al. (2012) demonstrated that Sema3E-PlexD1 signaling controls pathway-specific synapse formation in the striatum. The authors first find that PlexD1 is expressed by the direct pathway, but not the indirect pathway, MSNs, whereas Sema3E is expressed in the thalamus and in deep cortical layers, the two principal sources of glutamatergic inputs to the striatum (Ding et al., 2012). AMPA receptor-mediated spontaneous miniature excitatory postsynaptic currents (mEPSCs) were measured using the whole-cell voltage-clamp recording, and loss of either Sema3E or PlexD1 was found to lead to a large increase in mEPSC frequency, but not amplitude, in direct pathway MSNs (Ding et al., 2012). Furthermore, optogenetic activation of thalamostriatal axons showed that loss of PlexD1 or Sema3E leads to large evoked thalamostriatal EPSCs in the direct pathway MSNs, and loss of PlexD1 increases thalamostriatal synapse number (Ding et al., 2012). In thalamostriatal projections, Sema3E is secreted by axons and PlexD1 is expressed by postsynaptic neurons. Therefore, it is unlikely that Sema3E-PlexD1 signaling affects the targeting axons, as is observed in the spinal cord (Pecho-Vrieseling et al., 2009). Instead, Sema3E-PlexD1 signaling may control thalamostriatal synaptic strength by regulating postsynaptic sites through the PlexD1 receptor (Figure 5). For example, PlexD1 receptor signaling may alter the cytoskeleton or regulate glutamate receptor trafficking and stabilization. Alternatively, Sema3E-PlexD1 signaling may produce a secreted molecule to induce a retrograde signal in the postsynaptic sites that repels thalamostriatal axons.

Bottom Line: The major semaphorin receptors are plexins and neuropilins, however other receptors and co-receptors also mediate signaling by semaphorins.Upon semaphorin binding to their receptors, downstream signaling molecules transduce this event within cells to mediate further events, including alteration of microtubule and actin cytoskeletal dynamics.Here, I review recent studies on semaphorin signaling in vertebrate neural circuit assembly, with the goal of highlighting how this diverse family of cues and receptors imparts exquisite specificity to neural complex connectivity.

View Article: PubMed Central - PubMed

Affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center Cincinnati, OH, USA.

ABSTRACT
Neural circuit formation requires the coordination of many complex developmental processes. First, neurons project axons over long distances to find their final targets and then establish appropriate connectivity essential for the formation of neuronal circuitry. Growth cones, the leading edges of axons, navigate by interacting with a variety of attractive and repulsive axon guidance cues along their trajectories and at final target regions. In addition to guidance of axons, neuronal polarization, neuronal migration, and dendrite development must be precisely regulated during development to establish proper neural circuitry. Semaphorins consist of a large protein family, which includes secreted and cell surface proteins, and they play important roles in many steps of neural circuit formation. The major semaphorin receptors are plexins and neuropilins, however other receptors and co-receptors also mediate signaling by semaphorins. Upon semaphorin binding to their receptors, downstream signaling molecules transduce this event within cells to mediate further events, including alteration of microtubule and actin cytoskeletal dynamics. Here, I review recent studies on semaphorin signaling in vertebrate neural circuit assembly, with the goal of highlighting how this diverse family of cues and receptors imparts exquisite specificity to neural complex connectivity.

No MeSH data available.