Foxp4 is essential in maintenance of purkinje cell dendritic arborization in the mouse cerebellum

• Published in: Neuroscience Vol. 172; no. 1; pp. 562 - 571
• Main Authors: Tam, W.Y, Leung, C.K.Y, Tong, K.K, Kwan, K.M
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 13.01.2011; Elsevier
• Subjects: Animals; Animals, Newborn; Bergmann glial cell; Biological and medical sciences; Cell Communication - physiology; Cell Differentiation - physiology; Cell Shape - physiology; Cell Survival - physiology; Cerebellar Cortex - cytology; Cerebellar Cortex - growth & development; Cerebellar Cortex - metabolism; cerebellar slice culture; Dendrites - physiology; Forkhead Transcription Factors - deficiency; Forkhead Transcription Factors - physiology; Foxp4; Fundamental and applied biological sciences. Psychology; Gene Knockdown Techniques - methods; gene silencing; Mice; Mice, Inbred ICR; Neurogenesis - physiology; Neuroglia - cytology; Neuroglia - physiology; Neurology; Organ Culture Techniques; Purkinje cell; Purkinje Cells - cytology; Purkinje Cells - metabolism; RNA Interference - physiology; siRNA; Vertebrates: nervous system and sense organs; normal sheep serum; E; HRP; PFA; small interfering RNA; phosphate-buffered saline; P; BSA; reverse transcription-polymerase chain reaction; RT-PCR; horseradish peroxidase; embryonic day; postnatal day; Purkinje cell; paraformaldehyde; diaminobenzidine; PBS; Purkinje cell(s); DAB; gene silencing; siRNA; forkhead box; PC(s); Fox; cerebellar slice culture; GFAP; NSS; Bergmann glial cell; Foxp4; glial fibrillary acidic protein; bovine serum albumin; Cerebellum; Glial cell; Neuroglia; Rodentia; Central nervous system; Encephalon; Vertebrata; Mammalia; Mouse; Animal
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.10.023

Abstract Purkinje cells (PCs) are one of the principal neurons in the cerebellar cortex that play a central role in the coordination of fine-tuning body movement and balance. To acquire normal cerebellum function, PCs develop extensive dendritic arbors that establish synaptic connections with the parallel fibers of granule cells to form the proper neuronal circuitry. Therefore, dendritic arborization of PCs is an important developmental step to construct the mature neural network in the cerebellum. However, the genetic control of this process is not fully understood. In this study, Foxp4 , a forkhead transcription factor that is expressed specifically in migrating and mature PCs of cerebellum from embryonic stages to adulthood, was knocked down by small interfering RNA (siRNA) in organotypic cerebellar slice culture. When Foxp4 expression was knocked down at postnatal day 5 (P5), no abnormalities for early dendritic remodeling of PCs were observed. However, when Foxp4 was knocked down in P10 cerebellar slices, the organization of PC dendritic arbors was highly impaired, leaving hypoplastic but non-apoptotic cell bodies. The radial alignment of Bergmann glial fibers that associated with PC dendrites was also lost. These results suggest that Foxp4 is dispensable for the early PC dendrite outgrowth, but is essential for the maintenance of PC dendritic arborization and subsequent association with Bergmann glial fibers.