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Patterns of neurogenesis and amplitude of Reelin expression are essential for making a mammalian-type cortex.

Nomura T, Takahashi M, Hara Y, Osumi N - PLoS ONE (2008)

Bottom Line: We compared the neurogenesis in mammalian and avian pallium, focusing on subtype-specific gene expression, and found that the avian pallium generates distinct types of neurons in a spatially restricted manner.Furthermore, expression of Reelin gene is hardly detected in the developing avian pallium, and an experimental increase in Reelin-positive cells in the avian pallium modified radial fiber organization, which resulted in dramatic changes in the morphology of migrating neurons.Our results demonstrate that distinct mechanisms govern the patterns of neuronal specification in mammalian and avian pallial development, and that Reelin-dependent neuronal migration plays a critical role in mammalian type corticogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of Developmental Neuroscience, Center for Translational and Advanced Animal Research (CTTAR), Tohoku University School of Medicine, Sendai, Japan.

ABSTRACT
The mammalian neocortex is characterized as a six-layered laminar structure, in which distinct types of pyramidal neurons are distributed coordinately during embryogenesis. In contrast, no other vertebrate class possesses a brain region that is strictly analogous to the neocortical structure. Although it is widely accepted that the pallium, a dorsal forebrain region, is specified in all vertebrate species, little is known of the differential mechanisms underlying laminated or non-laminated structures in the pallium. Here we show that differences in patterns of neuronal specification and migration provide the pallial architectonic diversity. We compared the neurogenesis in mammalian and avian pallium, focusing on subtype-specific gene expression, and found that the avian pallium generates distinct types of neurons in a spatially restricted manner. Furthermore, expression of Reelin gene is hardly detected in the developing avian pallium, and an experimental increase in Reelin-positive cells in the avian pallium modified radial fiber organization, which resulted in dramatic changes in the morphology of migrating neurons. Our results demonstrate that distinct mechanisms govern the patterns of neuronal specification in mammalian and avian pallial development, and that Reelin-dependent neuronal migration plays a critical role in mammalian type corticogenesis. These lines of evidence shed light on the developmental programs underlying the evolution of the mammalian specific laminated cortex.

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A role of Reelin-positive cells in the developing vertebrate pallium.(Left) Without Reelin-positive cells, radial glial cells (RG) extend fibers in multiple orientations. Neurons migrate independently, and exhibit a multi-polar shape (a, b). (Right) In the presence of Reelin-expressing cells at the pial surface (magenta), RG fibers are directed toward the source of Reelin. Migrating neurons shorten their own fibers for translocation (c) or attach to RG fibers for locomotion (d). Neurons exhibit a polarized shape during and after migration (e).
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pone-0001454-g008: A role of Reelin-positive cells in the developing vertebrate pallium.(Left) Without Reelin-positive cells, radial glial cells (RG) extend fibers in multiple orientations. Neurons migrate independently, and exhibit a multi-polar shape (a, b). (Right) In the presence of Reelin-expressing cells at the pial surface (magenta), RG fibers are directed toward the source of Reelin. Migrating neurons shorten their own fibers for translocation (c) or attach to RG fibers for locomotion (d). Neurons exhibit a polarized shape during and after migration (e).

Mentions: In the developing mammalian cortex, parallel elongated radial fibers play essential roles in radial neuronal migration, by serving as a migratory scaffold or an anchor for translocation, thereby giving rise to the columnar distribution of pyramidal neurons (reviewed in [3], [4], [43]). Several studies demonstrated that Reelin signaling regulates the extension and orientation of radial fibers [44], [45]. In the hippocampus of Reelin-signal deficient mice, radial fibers in the dentate granule cell layer randomly project, and a laminar structure is severely disrupted [45], [46]. However, exogenous Reelin refined radial fiber alignment as seen in normal mice, thereby laminar organization was restored [45]. Thus, straight extension of the radial fiber is prerequisite for laminar formation during mammalian brain development. It is not yet possible to state conclusively whether the unique feature of avian radial fibers is due to the absence of Reelin signaling or other unknown mechanisms. However, the present study provides significant evidence of the role of radial fibers in the pallial development across vertebrate species: contribution to the morphological conversion of migrating neurons. During mammalian cortical development, multi-polar to bipolar conversion is an essential step for migrating neurons to reach out the cortical plate [47], and to establish a highly polarized “pyramidal” shape [48]. In contrast, the avian pallial neurons always display multi-polar morphology, retaining symmetrical dendritic trees, during and after migration. Concomitantly, histological evidence indicates that the avian pallium is devoid of pyramidal neurons (reviewed in [13]. We propose that Reelin-dependent directed growth of radial fibers substantially contribute to the mammalian specific “pyramidal” shape of neurons (Fig. 8), in addition to direct roles of Reelin on the migrating neurons themselves [49], [50], and/or another cell intrinsic/extrinsic mechanisms for establishment of the neuronal polarity (reviewed in [51]). Although we could not eliminate a possibility that the morphological change of radial glial cells is due to secondary effects by Reelin or Dbx1 overexpression, future experiments such as functional blocking of Dab1 protein, which is an intracellular mediator of Reelin signaling [52], will clarify direct/indirect influences of Reelin on radial glial fibers.


Patterns of neurogenesis and amplitude of Reelin expression are essential for making a mammalian-type cortex.

Nomura T, Takahashi M, Hara Y, Osumi N - PLoS ONE (2008)

A role of Reelin-positive cells in the developing vertebrate pallium.(Left) Without Reelin-positive cells, radial glial cells (RG) extend fibers in multiple orientations. Neurons migrate independently, and exhibit a multi-polar shape (a, b). (Right) In the presence of Reelin-expressing cells at the pial surface (magenta), RG fibers are directed toward the source of Reelin. Migrating neurons shorten their own fibers for translocation (c) or attach to RG fibers for locomotion (d). Neurons exhibit a polarized shape during and after migration (e).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2175532&req=5

pone-0001454-g008: A role of Reelin-positive cells in the developing vertebrate pallium.(Left) Without Reelin-positive cells, radial glial cells (RG) extend fibers in multiple orientations. Neurons migrate independently, and exhibit a multi-polar shape (a, b). (Right) In the presence of Reelin-expressing cells at the pial surface (magenta), RG fibers are directed toward the source of Reelin. Migrating neurons shorten their own fibers for translocation (c) or attach to RG fibers for locomotion (d). Neurons exhibit a polarized shape during and after migration (e).
Mentions: In the developing mammalian cortex, parallel elongated radial fibers play essential roles in radial neuronal migration, by serving as a migratory scaffold or an anchor for translocation, thereby giving rise to the columnar distribution of pyramidal neurons (reviewed in [3], [4], [43]). Several studies demonstrated that Reelin signaling regulates the extension and orientation of radial fibers [44], [45]. In the hippocampus of Reelin-signal deficient mice, radial fibers in the dentate granule cell layer randomly project, and a laminar structure is severely disrupted [45], [46]. However, exogenous Reelin refined radial fiber alignment as seen in normal mice, thereby laminar organization was restored [45]. Thus, straight extension of the radial fiber is prerequisite for laminar formation during mammalian brain development. It is not yet possible to state conclusively whether the unique feature of avian radial fibers is due to the absence of Reelin signaling or other unknown mechanisms. However, the present study provides significant evidence of the role of radial fibers in the pallial development across vertebrate species: contribution to the morphological conversion of migrating neurons. During mammalian cortical development, multi-polar to bipolar conversion is an essential step for migrating neurons to reach out the cortical plate [47], and to establish a highly polarized “pyramidal” shape [48]. In contrast, the avian pallial neurons always display multi-polar morphology, retaining symmetrical dendritic trees, during and after migration. Concomitantly, histological evidence indicates that the avian pallium is devoid of pyramidal neurons (reviewed in [13]. We propose that Reelin-dependent directed growth of radial fibers substantially contribute to the mammalian specific “pyramidal” shape of neurons (Fig. 8), in addition to direct roles of Reelin on the migrating neurons themselves [49], [50], and/or another cell intrinsic/extrinsic mechanisms for establishment of the neuronal polarity (reviewed in [51]). Although we could not eliminate a possibility that the morphological change of radial glial cells is due to secondary effects by Reelin or Dbx1 overexpression, future experiments such as functional blocking of Dab1 protein, which is an intracellular mediator of Reelin signaling [52], will clarify direct/indirect influences of Reelin on radial glial fibers.

Bottom Line: We compared the neurogenesis in mammalian and avian pallium, focusing on subtype-specific gene expression, and found that the avian pallium generates distinct types of neurons in a spatially restricted manner.Furthermore, expression of Reelin gene is hardly detected in the developing avian pallium, and an experimental increase in Reelin-positive cells in the avian pallium modified radial fiber organization, which resulted in dramatic changes in the morphology of migrating neurons.Our results demonstrate that distinct mechanisms govern the patterns of neuronal specification in mammalian and avian pallial development, and that Reelin-dependent neuronal migration plays a critical role in mammalian type corticogenesis.

View Article: PubMed Central - PubMed

Affiliation: Division of Developmental Neuroscience, Center for Translational and Advanced Animal Research (CTTAR), Tohoku University School of Medicine, Sendai, Japan.

ABSTRACT
The mammalian neocortex is characterized as a six-layered laminar structure, in which distinct types of pyramidal neurons are distributed coordinately during embryogenesis. In contrast, no other vertebrate class possesses a brain region that is strictly analogous to the neocortical structure. Although it is widely accepted that the pallium, a dorsal forebrain region, is specified in all vertebrate species, little is known of the differential mechanisms underlying laminated or non-laminated structures in the pallium. Here we show that differences in patterns of neuronal specification and migration provide the pallial architectonic diversity. We compared the neurogenesis in mammalian and avian pallium, focusing on subtype-specific gene expression, and found that the avian pallium generates distinct types of neurons in a spatially restricted manner. Furthermore, expression of Reelin gene is hardly detected in the developing avian pallium, and an experimental increase in Reelin-positive cells in the avian pallium modified radial fiber organization, which resulted in dramatic changes in the morphology of migrating neurons. Our results demonstrate that distinct mechanisms govern the patterns of neuronal specification in mammalian and avian pallial development, and that Reelin-dependent neuronal migration plays a critical role in mammalian type corticogenesis. These lines of evidence shed light on the developmental programs underlying the evolution of the mammalian specific laminated cortex.

Show MeSH