Failed cytokinesis of neural progenitors in citron kinase-deficient rats leads to multiciliated neurons.
Most, if not all, cortical neurons possess a single primary cilium; however, little is known about the mechanisms that control neuronal ciliogenesis. The Citron kinase-deficient (Citron-K(fh/fh)) rat, a model in which failed cytokinesis during development produces cortical neurons containing multiple cellular organelles, provides a unique system in which to examine the relationship between centriole inheritance and neuronal ciliogenesis. In this study, we analyzed the cerebral cortex of these animals using immunohistochemistry, serial confocal, and electron microscopy to determine if the multinucleated neurons present in the cortex of these animals also possess multiple centrioles and cilia. We found that neurons containing multiple nuclei possessed multiple centrioles and cilia whose lengths varied across cortical regions. Despite the presence of multiple cilia, we found that perinatal expression of adenylyl cyclase III, a cilia-specific marker, and somatostatin receptor 3, a receptor enriched in cilia, were preserved in developing Citron-K(fh/fh) brain. Together, these results show that multinucleated neurons arising from defective cytokinesis can extend multiple cilia.
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610-0244, USA.
Sara B
SB
Anastas
Dorit
D
Mueller
Susan L
SL
Semple-Rowland
Joshua J
JJ
Breunig
Matthew R
MR
Sarkisian
D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D002923:Cilia / Q000502:physiology* / Q000648:ultrastructure; D048749:Cytokinesis / Q000235:genetics*; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency*; D018613:Microscopy, Confocal; D008854:Microscopy, Electron / Q000379:methods; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency*; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000378:metabolism; D013003:Somatosensory Cortex / Q000166:cytology*; D013234:Stem Cells / Q000378:metabolism* / Q000648:ultrastructure
D047908:Intracellular Signaling Peptides and Proteins; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases; D010751:Phosphopyruvate Hydratase