Loss of cell adhesion causes hydrocephalus in nonmuscle myosin II-B-ablated and mutated mice.
Ablation of nonmuscle myosin (NM) II-B in mice during embryonic development leads to marked enlargement of the cerebral ventricles and destruction of brain tissue, due to hydrocephalus. We have identified a transient mesh-like structure present at the apical border of cells lining the spinal canal of mice during development. This structure, which only contains the II-B isoform of NM, also contains beta-catenin and N-cadherin, consistent with a role in cell adhesion. Ablation of NM II-B or replacement of NM II-B with decreased amounts of a mutant (R709C), motor-impaired NM II-B in mice results in collapse of the mesh-like structure and loss of cell adhesion. This permits the underlying neuroepithelial cells to invade the spinal canal and obstruct cerebral spinal fluid flow. These defects in the CNS of NM II-B-ablated mice seem to be the cause of hydrocephalus. Interestingly, the mesh-like structure and patency of the spinal canal can be restored by increasing expression of the motor-impaired NM II-B, which also rescues hydrocephalus. However, the mutant isoform cannot completely rescue neuronal cell migration. These studies show that the scaffolding properties of NM II-B play an important role in cell adhesion, thereby preventing hydrocephalus during mouse brain development.
Ma
Xuefei
X
Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1762, USA. max@nhlbi.nih.gov
Bao
Jianjun
J
Adelstein
Robert S
RS
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000196:embryology / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement; D006801:Humans; D006849:Hydrocephalus / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D046569:Neuroepithelial Cells / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics / Q000378:metabolism*; D013115:Spinal Canal / Q000166:cytology*; D013116:Spinal Cord / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology
D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains