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Molecules and mechanisms that regulate multipolar migration in the intermediate zone.

Cooper JA - Front Cell Neurosci (2014)

Bottom Line: This reorientation implies the existence of directional signals in the IZ that are ignored during the multipolar stage but sensed after axonogenesis.Other signals are implicated in starting multipolar migration and triggering axon outgrowth.Here we review the molecules and mechanisms that regulate multipolar migration, and also discuss how multipolar migration affects the orderly arrangement of neurons in layers and columns in the developing neocortex.

View Article: PubMed Central - PubMed

Affiliation: Fred Hutchinson Cancer Research Center, Division of Basic Sciences Seattle, Washington, USA.

ABSTRACT
Most neurons migrate with an elongated, "bipolar" morphology, extending a long leading process that explores the environment. However, when immature projection neurons enter the intermediate zone (IZ) of the neocortex they become "multipolar". Multipolar cells extend and retract cytoplasmic processes in different directions and move erratically-sideways, up and down. Multipolar cells extend axons while they are in the lower half of the IZ. Remarkably, the cells then resume radial migration: they reorient their centrosome and Golgi apparatus towards the pia, transform back to bipolar morphology, and commence locomotion along radial glia (RG) fibers. This reorientation implies the existence of directional signals in the IZ that are ignored during the multipolar stage but sensed after axonogenesis. In vivo genetic manipulation has implicated a variety of candidate directional signals, cell surface receptors, and signaling pathways, that may be involved in polarizing multipolar cells and stabilizing a pia-directed leading process for radial migration. Other signals are implicated in starting multipolar migration and triggering axon outgrowth. Here we review the molecules and mechanisms that regulate multipolar migration, and also discuss how multipolar migration affects the orderly arrangement of neurons in layers and columns in the developing neocortex.

No MeSH data available.


Phases of migration of neocortical projection neurons. Principal phases of migration: (1), movement from the VZ to the IZ/SVZ with bipolar or “pin-like” morphology; (2), multipolar migration; (3), bipolar locomotion along radial glia (RG); (4), terminal translocation. Multipolar migration can be subdivided into further stages: 2A, initial multipolar migration of newborn post-mitotic neurons and intermediate progenitors; 2A’, division of intermediate progenitors followed by multipolar migration; 2B, axon emergence and growth; 2C, stabilization of a dominant pia-directed leading process. The left-hand side shows the principal divisions of the cortex (VZ, ventricular zone; IZ/SVZ, intermediate/subventricular zone; CP, cortical plate; MZ, marginal zone). The right-hand side indicates the major features of the local environment through which neurons migrate. See text for details.
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Figure 1: Phases of migration of neocortical projection neurons. Principal phases of migration: (1), movement from the VZ to the IZ/SVZ with bipolar or “pin-like” morphology; (2), multipolar migration; (3), bipolar locomotion along radial glia (RG); (4), terminal translocation. Multipolar migration can be subdivided into further stages: 2A, initial multipolar migration of newborn post-mitotic neurons and intermediate progenitors; 2A’, division of intermediate progenitors followed by multipolar migration; 2B, axon emergence and growth; 2C, stabilization of a dominant pia-directed leading process. The left-hand side shows the principal divisions of the cortex (VZ, ventricular zone; IZ/SVZ, intermediate/subventricular zone; CP, cortical plate; MZ, marginal zone). The right-hand side indicates the major features of the local environment through which neurons migrate. See text for details.

Mentions: Four phases of projection neuron migration have been described through detailed histological and live imaging studies (Shoukimas and Hinds, 1978; O’Rourke et al., 1992; Nadarajah et al., 2001; Hatanaka and Murakami, 2002; Tabata and Nakajima, 2003; Hatanaka et al., 2004, 2009; Noctor et al., 2004; Ochiai et al., 2007; de Anda et al., 2010; Namba et al., 2014; Figure 1). In phase 1, asymmetric division of radial glia progenitors (RG) in the VZ creates new post-mitotic neurons and intermediate progenitors (IP). These cells exit the VZ with bipolar or “pin-like” morphology. Phase 2 starts when cells reach the subventricular zone (SVZ)/IZ and become multipolar (Figure 1, stage 2A). MP IP divide in the SVZ and their daughters resume MP migration (stage 2A’). After a day or more in the MP phase, a ventricle- or horizontally-oriented process near the centrosome begins to extend and becomes the axon (stage 2B). Phase 2 ends when the MP cell reorients the Golgi and centrosome towards the pia, establishes a dominant pia-directed leading process, and starts radial migration, trailing the axon behind (Hatanaka et al., 2004; de Anda et al., 2010) (stage 2C). This is known at the multipolar to bipolar (MP-BP) transition, and requires the stabilization of a dominant leading process and the correct orientation of that process towards the pia. After the MP-BP transition, neurons rapidly exit the IZ by locomotion along RG (phase 3), followed by phase 4, terminal translocation to the top of the CP.


Molecules and mechanisms that regulate multipolar migration in the intermediate zone.

Cooper JA - Front Cell Neurosci (2014)

Phases of migration of neocortical projection neurons. Principal phases of migration: (1), movement from the VZ to the IZ/SVZ with bipolar or “pin-like” morphology; (2), multipolar migration; (3), bipolar locomotion along radial glia (RG); (4), terminal translocation. Multipolar migration can be subdivided into further stages: 2A, initial multipolar migration of newborn post-mitotic neurons and intermediate progenitors; 2A’, division of intermediate progenitors followed by multipolar migration; 2B, axon emergence and growth; 2C, stabilization of a dominant pia-directed leading process. The left-hand side shows the principal divisions of the cortex (VZ, ventricular zone; IZ/SVZ, intermediate/subventricular zone; CP, cortical plate; MZ, marginal zone). The right-hand side indicates the major features of the local environment through which neurons migrate. See text for details.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4231986&req=5

Figure 1: Phases of migration of neocortical projection neurons. Principal phases of migration: (1), movement from the VZ to the IZ/SVZ with bipolar or “pin-like” morphology; (2), multipolar migration; (3), bipolar locomotion along radial glia (RG); (4), terminal translocation. Multipolar migration can be subdivided into further stages: 2A, initial multipolar migration of newborn post-mitotic neurons and intermediate progenitors; 2A’, division of intermediate progenitors followed by multipolar migration; 2B, axon emergence and growth; 2C, stabilization of a dominant pia-directed leading process. The left-hand side shows the principal divisions of the cortex (VZ, ventricular zone; IZ/SVZ, intermediate/subventricular zone; CP, cortical plate; MZ, marginal zone). The right-hand side indicates the major features of the local environment through which neurons migrate. See text for details.
Mentions: Four phases of projection neuron migration have been described through detailed histological and live imaging studies (Shoukimas and Hinds, 1978; O’Rourke et al., 1992; Nadarajah et al., 2001; Hatanaka and Murakami, 2002; Tabata and Nakajima, 2003; Hatanaka et al., 2004, 2009; Noctor et al., 2004; Ochiai et al., 2007; de Anda et al., 2010; Namba et al., 2014; Figure 1). In phase 1, asymmetric division of radial glia progenitors (RG) in the VZ creates new post-mitotic neurons and intermediate progenitors (IP). These cells exit the VZ with bipolar or “pin-like” morphology. Phase 2 starts when cells reach the subventricular zone (SVZ)/IZ and become multipolar (Figure 1, stage 2A). MP IP divide in the SVZ and their daughters resume MP migration (stage 2A’). After a day or more in the MP phase, a ventricle- or horizontally-oriented process near the centrosome begins to extend and becomes the axon (stage 2B). Phase 2 ends when the MP cell reorients the Golgi and centrosome towards the pia, establishes a dominant pia-directed leading process, and starts radial migration, trailing the axon behind (Hatanaka et al., 2004; de Anda et al., 2010) (stage 2C). This is known at the multipolar to bipolar (MP-BP) transition, and requires the stabilization of a dominant leading process and the correct orientation of that process towards the pia. After the MP-BP transition, neurons rapidly exit the IZ by locomotion along RG (phase 3), followed by phase 4, terminal translocation to the top of the CP.

Bottom Line: This reorientation implies the existence of directional signals in the IZ that are ignored during the multipolar stage but sensed after axonogenesis.Other signals are implicated in starting multipolar migration and triggering axon outgrowth.Here we review the molecules and mechanisms that regulate multipolar migration, and also discuss how multipolar migration affects the orderly arrangement of neurons in layers and columns in the developing neocortex.

View Article: PubMed Central - PubMed

Affiliation: Fred Hutchinson Cancer Research Center, Division of Basic Sciences Seattle, Washington, USA.

ABSTRACT
Most neurons migrate with an elongated, "bipolar" morphology, extending a long leading process that explores the environment. However, when immature projection neurons enter the intermediate zone (IZ) of the neocortex they become "multipolar". Multipolar cells extend and retract cytoplasmic processes in different directions and move erratically-sideways, up and down. Multipolar cells extend axons while they are in the lower half of the IZ. Remarkably, the cells then resume radial migration: they reorient their centrosome and Golgi apparatus towards the pia, transform back to bipolar morphology, and commence locomotion along radial glia (RG) fibers. This reorientation implies the existence of directional signals in the IZ that are ignored during the multipolar stage but sensed after axonogenesis. In vivo genetic manipulation has implicated a variety of candidate directional signals, cell surface receptors, and signaling pathways, that may be involved in polarizing multipolar cells and stabilizing a pia-directed leading process for radial migration. Other signals are implicated in starting multipolar migration and triggering axon outgrowth. Here we review the molecules and mechanisms that regulate multipolar migration, and also discuss how multipolar migration affects the orderly arrangement of neurons in layers and columns in the developing neocortex.

No MeSH data available.