title: A role for atypical cadherin Celsr3 in hippocampal maturation and connectivity.
abstract: Atypical cadherin Celsr3, a regulator of planar cell polarity, is critical for the development of the axonal blueprint. We previously showed that expression of Celsr3 is necessary to establish forebrain connections such as the anterior commissure and thalamocortical and corticospinal tracts. The requirement for Celsr3 during hippocampal wiring and its action in the hippocampus remain largely unexplored. Here, we compared the connectivity and maturation of the hippocampal formation in Celsr3|Foxg1 and Celsr3|Dlx mice. Celsr3 is inactivated in the whole telencephalon, including the hippocampal primordium, in Celsr3|Foxg1 mice, and in the early basal telencephalon, including ganglionic eminences and ventral diencephalon, in Celsr3|Dlx mice. Behavioral tests showed that both mutants were hyperactive and had impaired learning and memory. Abnormal cytoarchitecture of CA1, CA3, and dentate gyrus was found in the Celsr3|Foxg1 mutant, in which afferent and efferent hippocampal pathways, as well as intrinsic connections, were dramatically disrupted. In Celsr3|Dlx mutant mice, hippocampal cytoarchitecture was mildly affected and extrinsic and intrinsic connectivity moderately disturbed. In both mutants, pyramidal neurons in CA1 harbored atrophic dendritic trees, with decreased synapse density and increased proportion of symmetric versus asymmetric synapses, and long-term potentiation was altered. In contrast, mutant hippocampal neurons extended neurites that were normal, even longer than those of control neurons, indicating that anomalies in vivo are secondary to defective connections. Postnatal neurogenesis was preserved and mutant interneurons were able to migrate to the hippocampus. Thus, like in neocortex, Celsr3 is required for hippocampal development, connectivity and function, and for pyramidal cell maturation.
authors.affiliation: Joint Laboratory for Brain Function and Health, Jinan University and the University of Hong Kong, Medical School of Jinan University, Guangzhou 510632, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Feng
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Meizhi
authors.initials: M
authors.lastname: Wang
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Ruan
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.forename: Fadel
authors.initials: F
authors.lastname: Tissir
authors.forename: Andre
authors.initials: A
authors.lastname: Goffinet
authors.forename: Libing
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000818:Animals; D015820:Cadherins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured / Q000378:metabolism / Q000648:ultrastructure; D003712:Dendrites / Q000648:ultrastructure; D005260:Female; D005456:Fluorescent Dyes; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D006624:Hippocampus / Q000196:embryology* / Q000254:growth & development / Q000502:physiology / Q000648:ultrastructure; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D006948:Hyperkinesis / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D007395:Interneurons / Q000502:physiology; D007859:Learning Disabilities / Q000235:genetics* / Q000473:pathology; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000235:genetics* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D009434:Neural Pathways / Q000648:ultrastructure*; D055495:Neurogenesis; D017966:Pyramidal Cells / Q000502:physiology* / Q000648:ultrastructure; D011930:Reaction Time; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000648:ultrastructure; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: D015820:Cadherins; C444454:Celsr3 protein, mouse; C088334:Distal-less homeobox proteins; D005456:Fluorescent Dyes; D051858:Forkhead Transcription Factors; C489565:Foxg1 protein, mouse; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D014157:Transcription Factors