Structural abnormalities develop in the brain after ablation of the gene encoding nonmuscle myosin II-B heavy chain.
Ablation of nonmuscle myosin heavy chain II-B (NMHC-B) in mice results in severe hydrocephalus with enlargement of the lateral and third ventricles. All B(-)/B(-) mice died either during embryonic development or on the day of birth (PO). Neurons cultured from superior cervical ganglia of B(-)/B(-) mice between embryonic day (E) 18 and P0 showed decreased rates of neurite outgrowth, and their growth cones had a distinctive narrow morphology compared with those from normal mice. Serial sections of E12.5, E13.5, and E15 mouse brains identified developmental defects in the ventricular neuroepithelium. On E12.5, disruption of the coherent ventricular surface and disordered cell migration of neuroepithelial and differentiated cells were seen at various points in the ventricular walls. These abnormalities resulted in the formation of rosettes in various regions of the brain and spinal cord. On E13.5 and E15, disruption of the ventricular surface and aberrant protrusions of neural cells into the ventricles became more prominent. By E18.5 and P0, the defects in cells lining the ventricular wall resulted in an obstructive hydrocephalus due to stenosis or occlusion of the third ventricle and cerebral aqueduct. These defects may be caused by abnormalities in the cell adhesive properties of neuroepithelial cells and suggest that NMHC-B is essential for both early and late developmental processes in the mammalian brain.
Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
A N
AN
Tullio
P C
PC
Bridgman
N J
NJ
Tresser
C C
CC
Chan
M A
MA
Conti
R S
RS
Adelstein
Y
Y
Hara
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000002:abnormalities*; D003599:Cytoskeleton / Q000473:pathology; D005260:Female; D005333:Fetus / Q000002:abnormalities; D006849:Hydrocephalus / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D018995:Myosin Heavy Chains / Q000235:genetics*; D009218:Myosins / Q000235:genetics*; D009474:Neurons / Q000166:cytology; D011247:Pregnancy
D018995:Myosin Heavy Chains; D009218:Myosins