Regulation of radial glial survival by signals from the meninges.
Radial glial cells (RGCs) in the developing cerebral cortex are progenitors for neurons and glia, and their processes serve as guideposts for migrating neurons. So far, it has remained unclear whether RGC processes also control the function of RGCs more directly. Here, we show that RGC numbers and cortical size are reduced in mice lacking beta1 integrins in RGCs. TUNEL stainings and time-lapse video recordings demonstrate that beta1-deficient RGCs processes detach from the meningeal basement membrane (BM) followed by apoptotic death of RGCs. Apoptosis is also induced by surgical removal of the meninges. Finally, mice lacking the BM components laminin alpha2 and alpha4 show defects in the attachment of RGC processes at the meninges, a reduction in cortical size, and enhanced apoptosis of RGC cells. Our findings demonstrate that attachment of RGC processes at the meninges is important for RGC survival and the control of cortical size.
Radakovits
Randor
R
The Scripps Research Institute, Department of Cell Biology, Institute for Childhood and Neglected Disease, La Jolla, California 92037, USA.
Barros
Claudia S
CS
Belvindrah
Richard
R
Patton
Bruce
B
Müller
Ulrich
U
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000254:growth & development; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D005136:Eye Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D066298:In Vitro Techniques; D019426:Integrases / Q000235:genetics; D019012:Integrin beta1 / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000172:deficiency; D007797:Laminin / Q000235:genetics; D008578:Meninges / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency; D064231:Nestin; D055495:Neurogenesis / Q000502:physiology; D009457:Neuroglia / Q000502:physiology*; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism
D005136:Eye Proteins; D018398:Homeodomain Proteins; D019012:Integrin beta1; D007381:Intermediate Filament Proteins; C501370:Lama4 protein, mouse; D007797:Laminin; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; C485184:enhanced green fluorescent protein; C102645:laminin alpha 2; D049452:Green Fluorescent Proteins; C045073:Cre recombinase; D019426:Integrases; D001973:Bromodeoxyuridine