Meningeal cells stimulate neuronal migration and the formation of radial glial fascicles from the cerebellar external granular layer

The polarity and organization of radial glial cells (RGCs), which serve as both stem cells and scaffolds for neuronal migration, are crucial for cortical development. However, the cytoskeletal mechanisms that drive radial glial outgrowth and maintain RGC polarity remain poorly understood. Here, we show that the Arp2/3 complex, the unique actin nucleator that produces branched actin networks, plays essential roles in RGC polarity and morphogenesis. Disruption of the Arp2/3 complex in RGCs retards process outgrowth toward the basal surface and impairs apical polarity and adherens junctions. Whereas the former is correlated with abnormal actin-based leading edge, the latter is consistent with blockage in membrane trafficking. These defects result in altered cell fate, disrupted cortical lamination and abnormal angiogenesis. In addition, we present evidence that the Arp2/3 complex is a cell-autonomous regulator of neuronal migration. Our data suggest that Arp2/3-mediated actin assembly may be particularly important for neuronal cell motility in soft or poorly adhesive matrix environment.

Download Full-text

Prenatal treatment with metronidazole induces cerebellar folia alteration in guinea pig fetuses

Archives of Biological Sciences ◽

10.2298/abs200619041c ◽

2020 ◽

Vol 72 (4) ◽

pp. 473-482

Author(s):

Ivan Capo ◽

Ivan Milenkovic ◽

Natasa Capo ◽

Nebojsa Stilinovic ◽

Sasa Vukmirovic ◽

...

Keyword(s):

Animal Studies ◽

Granular Layer ◽

Molecular Layer ◽

Sensitive Period ◽

Insufficient Data ◽

Prenatal Treatment ◽

External Granular Layer ◽

Areal Fraction ◽

Experimental Group ◽

Partial Atrophy

The most sensitive period in brain development is during prenatal life. The use of antibiotics in pregnancy is still controversial. Recent studies revealed the high neurotoxic potential of the antibiotic and antiprotozoal medication, metronidazole. However, there are insufficient data from animal studies about prenatal treatment effects. We investigated the effect of prenatal treatment with metronidazole on cerebellar development in guinea pigs. Treatment with metronidazole was performed from the 42nd to the 49th day of gestation. On the 50th day of pregnancy, all dams were killed, and the cerebella of the fetuses were analyzed. Gross cerebellar changes characterized by malposition of the folia with partial atrophy were found in 12 of 19 fetuses in the experimental group, but in none of 20 control fetuses that received saline. The most affected were folia VII with depletion of the areal fraction of the external granular layer, molecular layer and the internal granular layer. Purkinje cells displayed cell distortion with loss of normal dendritic polarity. The investigation revealed cell depletion, with a disturbance of the cytoarchitectonic of the cerebellar cortex and folia alteration.

Download Full-text

Topical Review: Neuronal Migration in Cortical Development

Journal of Child Neurology ◽

10.1177/08830738040190030201 ◽

2004 ◽

Vol 19 (3) ◽

pp. 274-279

Author(s):

Shigeaki Kanatani ◽

Hidenori Tabata ◽

Kazunori Nakajima

Keyword(s):

Neuronal Migration ◽

Radial Glia ◽

Asymmetric Cell Division ◽

Time Lapse ◽

Radial Glial Cells ◽

Daughter Cells ◽

Radial Glial ◽

Time Lapse Imaging ◽

Mitotic Behavior

Cortical formation in the developing brain is a highly complicated process involving neuronal production (through symmetric or asymmetric cell division) interaction of radial glia with neuronal migration, and multiple modes of neuronal migration. It has been convincingly demonstrated by numerous studies that radial glial cells are neural stem cells. However, the processes by which neurons arise from radial glia and migrate to their final destinations in vivo are not yet fully understood. Recent studies using time-lapse imaging of neuronal migration are giving investigators an increasingly more detailed understanding of the mitotic behavior of radial glia and the migrating behavior of their daughter cells. In this review, we describe recent progress in elucidating neuronal migration in brain formation and how neuronal migration is disturbed by mutations in genes that control this process. ( J Child Neurol 2005;20:274—279).

Download Full-text