A normal radial glial scaffold is necessary for migration of interneurons during neocortical development.
The relationship between radial glia and neurons migrating tangentially from the ganglionic eminence (GE) has been suggested but not firmly established. To study this relationship we used a ferret model of cortical dysplasia where radial glia are highly disorganized. To produce this, an antimitotic, methylazoxy methanol (MAM) is injected on the 24th day of gestation (E24 MAM). Neurons migrating away from the GE in MAM-treated animals tend to remain in the intermediate zone (IZ) and do not reach the cortical plate (CP) as they do in normal ferret slices. We recently observed that the disrupted radial glia after MAM treatment could be restored toward their normal morphology by exogenous application of neuregulin1 (NRG1). We demonstrate here that when E24 MAM slices are treated with NRG1, the distribution of cells arising from the GE was similar to normal slices. In a second paradigm, we disrupted radial glia by adding ciliary neurotrophic factor (CNTF) to the culture media of normal ferret slices; CNTF induces acute differentiation of radial glia into astrocytes. After CNTF exposure, few tangentially migrating cells reach the CP compared to untreated slices. These results show that interneurons fail to reach the CP by disrupted normal radial glia and restoring the normal radial glial scaffold is sufficient to allow migrating cells to invade the CP. Our results suggest an important role for radial glia by controlling directly or indirectly the migration of interneurons to the CP, their main target.
Poluch
Sylvie
S
Department of Anatomy, Physiology, and Genetics, and Program in Neuroscience, USUHS, Bethesda, Maryland, USA.
Juliano
Sharon L
SL
D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D005289:Ferrets; D016130:Immunophenotyping; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism; D008746:Methylazoxymethanol Acetate / Q000031:analogs & derivatives / Q000633:toxicity; D019579:Neocortex / Q000002:abnormalities / Q000166:cytology* / Q000196:embryology*; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D013723:Teratogens; D005680:gamma-Aminobutyric Acid; D008746:Methylazoxymethanol Acetate; C030667:methylazoxymethanol