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Morphological and functional aspects of progenitors perturbed in cortical malformations.

Bizzotto S, Francis F - Front Cell Neurosci (2015)

Bottom Line: We describe how the particular morphology of these cells is related to their roles in the orchestration of cortical development and their influence on other progenitor types and post-mitotic neurons.The multiple recent entry points from human genetics and animal models are contributing to our understanding of this important cell type.Going beyond this, we discuss future directions that may provide new data in this expanding area.

View Article: PubMed Central - PubMed

Affiliation: INSERM UMRS 839 Paris, France ; Sorbonne Universités, Université Pierre et Marie Curie Paris, France ; Institut du Fer à Moulin Paris, France.

ABSTRACT
In this review, we discuss molecular and cellular mechanisms important for the function of neuronal progenitors during development, revealed by their perturbation in different cortical malformations. We focus on a class of neuronal progenitors, radial glial cells (RGCs), which are renowned for their unique morphological and behavioral characteristics, constituting a key element during the development of the mammalian cerebral cortex. We describe how the particular morphology of these cells is related to their roles in the orchestration of cortical development and their influence on other progenitor types and post-mitotic neurons. Important for disease mechanisms, we overview what is currently known about RGC cellular components, cytoskeletal mechanisms, signaling pathways and cell cycle characteristics, focusing on how defects lead to abnormal development and cortical malformation phenotypes. The multiple recent entry points from human genetics and animal models are contributing to our understanding of this important cell type. Combining data from phenotypes in the mouse reveals molecules which potentially act in common pathways. Going beyond this, we discuss future directions that may provide new data in this expanding area.

No MeSH data available.


Related in: MedlinePlus

Radial glial cell and different genes. Schematic representation of interphase and dividing RGCs (in green) and neurons (in gray) migrating along basal RGC processes. Higher magnifications show RGC structural details such as basal attachment to the pial surface (represented in red), apically located adherens junctions (black), apical attachments and midbody (purple), centrosomes (pink), primary cilia (blue), and a mitotic cell with the MTs organized in the mitotic spindle (light blue) and the DNA aligned at the metaphase plate (black). The ventricular surface is represented as a gray line. The different genes are represented close to the structure in which they have clearly been shown to be involved based on the classification proposed in this review, with a color corresponding to the color of the structure. Genes involved in RGC basal process attachment to the pial surface are represented in red; in black are genes linked with adherens junctions; in purple are genes participating in apical polarity, attachment to the ventricular surface, and in the apically-located midbody; in blue are genes essential for the primary cilium; in pink are represented centrosome-related genes, and in light blue genes participating in the regulation of mitotic spindle function. Genes that are involved in transcriptional regulation are represented in green.
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Figure 3: Radial glial cell and different genes. Schematic representation of interphase and dividing RGCs (in green) and neurons (in gray) migrating along basal RGC processes. Higher magnifications show RGC structural details such as basal attachment to the pial surface (represented in red), apically located adherens junctions (black), apical attachments and midbody (purple), centrosomes (pink), primary cilia (blue), and a mitotic cell with the MTs organized in the mitotic spindle (light blue) and the DNA aligned at the metaphase plate (black). The ventricular surface is represented as a gray line. The different genes are represented close to the structure in which they have clearly been shown to be involved based on the classification proposed in this review, with a color corresponding to the color of the structure. Genes involved in RGC basal process attachment to the pial surface are represented in red; in black are genes linked with adherens junctions; in purple are genes participating in apical polarity, attachment to the ventricular surface, and in the apically-located midbody; in blue are genes essential for the primary cilium; in pink are represented centrosome-related genes, and in light blue genes participating in the regulation of mitotic spindle function. Genes that are involved in transcriptional regulation are represented in green.

Mentions: As RGCs present a very specialized morphology and dynamics, which are strictly linked with the function they exert during cortex development, every minor perturbation involving their structure or behavior is susceptible to lead to major developmental problems. Indeed, numerous genes coding for proteins influencing RGC morphology and function have been found mutated in mouse models and in cortical malformation patients. We try to bring together here mouse mutant data related to these genes (also resumed in Table 2), classifying these data by different RGC compartments and cellular mechanisms (resumed in Figures 2, 3).


Morphological and functional aspects of progenitors perturbed in cortical malformations.

Bizzotto S, Francis F - Front Cell Neurosci (2015)

Radial glial cell and different genes. Schematic representation of interphase and dividing RGCs (in green) and neurons (in gray) migrating along basal RGC processes. Higher magnifications show RGC structural details such as basal attachment to the pial surface (represented in red), apically located adherens junctions (black), apical attachments and midbody (purple), centrosomes (pink), primary cilia (blue), and a mitotic cell with the MTs organized in the mitotic spindle (light blue) and the DNA aligned at the metaphase plate (black). The ventricular surface is represented as a gray line. The different genes are represented close to the structure in which they have clearly been shown to be involved based on the classification proposed in this review, with a color corresponding to the color of the structure. Genes involved in RGC basal process attachment to the pial surface are represented in red; in black are genes linked with adherens junctions; in purple are genes participating in apical polarity, attachment to the ventricular surface, and in the apically-located midbody; in blue are genes essential for the primary cilium; in pink are represented centrosome-related genes, and in light blue genes participating in the regulation of mitotic spindle function. Genes that are involved in transcriptional regulation are represented in green.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325918&req=5

Figure 3: Radial glial cell and different genes. Schematic representation of interphase and dividing RGCs (in green) and neurons (in gray) migrating along basal RGC processes. Higher magnifications show RGC structural details such as basal attachment to the pial surface (represented in red), apically located adherens junctions (black), apical attachments and midbody (purple), centrosomes (pink), primary cilia (blue), and a mitotic cell with the MTs organized in the mitotic spindle (light blue) and the DNA aligned at the metaphase plate (black). The ventricular surface is represented as a gray line. The different genes are represented close to the structure in which they have clearly been shown to be involved based on the classification proposed in this review, with a color corresponding to the color of the structure. Genes involved in RGC basal process attachment to the pial surface are represented in red; in black are genes linked with adherens junctions; in purple are genes participating in apical polarity, attachment to the ventricular surface, and in the apically-located midbody; in blue are genes essential for the primary cilium; in pink are represented centrosome-related genes, and in light blue genes participating in the regulation of mitotic spindle function. Genes that are involved in transcriptional regulation are represented in green.
Mentions: As RGCs present a very specialized morphology and dynamics, which are strictly linked with the function they exert during cortex development, every minor perturbation involving their structure or behavior is susceptible to lead to major developmental problems. Indeed, numerous genes coding for proteins influencing RGC morphology and function have been found mutated in mouse models and in cortical malformation patients. We try to bring together here mouse mutant data related to these genes (also resumed in Table 2), classifying these data by different RGC compartments and cellular mechanisms (resumed in Figures 2, 3).

Bottom Line: We describe how the particular morphology of these cells is related to their roles in the orchestration of cortical development and their influence on other progenitor types and post-mitotic neurons.The multiple recent entry points from human genetics and animal models are contributing to our understanding of this important cell type.Going beyond this, we discuss future directions that may provide new data in this expanding area.

View Article: PubMed Central - PubMed

Affiliation: INSERM UMRS 839 Paris, France ; Sorbonne Universités, Université Pierre et Marie Curie Paris, France ; Institut du Fer à Moulin Paris, France.

ABSTRACT
In this review, we discuss molecular and cellular mechanisms important for the function of neuronal progenitors during development, revealed by their perturbation in different cortical malformations. We focus on a class of neuronal progenitors, radial glial cells (RGCs), which are renowned for their unique morphological and behavioral characteristics, constituting a key element during the development of the mammalian cerebral cortex. We describe how the particular morphology of these cells is related to their roles in the orchestration of cortical development and their influence on other progenitor types and post-mitotic neurons. Important for disease mechanisms, we overview what is currently known about RGC cellular components, cytoskeletal mechanisms, signaling pathways and cell cycle characteristics, focusing on how defects lead to abnormal development and cortical malformation phenotypes. The multiple recent entry points from human genetics and animal models are contributing to our understanding of this important cell type. Combining data from phenotypes in the mouse reveals molecules which potentially act in common pathways. Going beyond this, we discuss future directions that may provide new data in this expanding area.

No MeSH data available.


Related in: MedlinePlus