Apoptosis and brain development.
Neuronal cell death in the embryonic brain was first recognized almost a century ago. Its significance for normal nervous system development and function has been a major focus of neuroscientific investigation ever since. Remarkable progress has been made in defining the cellular processes controlling neuronal cell death and studies performed over the last ten years have revealed extensive homology between the molecules regulating programmed cell death in Caenorhabditis elegans and apoptosis in mammalian cells. Targeted gene disruptions of members of the bcl-2 and caspase gene families have demonstrated particularly significant roles for bcl-x, bax, caspase-9 and caspase-3 in mammalian brain development. As expected from previous studies of synapse-bearing neurons and neurotrophic factors, reduced neuronal cell death in mice bearing mutations in key pro-apoptotic molecules resulted in increased numbers of neurons in a variety of neuronal subpopulations. However, targeted gene disruptions also demonstrated a heretofore underappreciated significance of neural precursor cell death and immature neuron death in nervous system development. Pathological activation of apoptotic death pathways may lead to neuroanatomic abnormalities and possibly to developmental disabilities.
Roth
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Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. kroth@pathbox.wustl.edu
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D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D053477:Apoptotic Protease-Activating Factor 1; D001921:Brain / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D019254:Genes, bcl-2 / Q000235:genetics; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling / Q000379:methods; D051379:Mice; D008817:Mice, Mutant Strains; D009434:Neural Pathways / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000235:genetics; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism / Q000648:ultrastructure; D013687:Telencephalon / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D051020:bcl-X Protein
C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; C494812:Bcl2l1 protein, mouse; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D020169:Caspases