title: Temporal expression and mitochondrial localization of a Foxp2 isoform lacking the forkhead domain in developing Purkinje cells.
abstract: FOXP2, a forkhead box-containing transcription factor, forms homo- or hetero-dimers with FOXP family members and localizes to the nucleus, while FOXP2(R553H), which contains a mutation related to speech/language disorders, features reduced DNA binding activity and both cytoplasmic and nuclear localization. In addition to being a loss-of-function mutation, it is possible that FOXP2(R553H) also may act as a gain-of-function mutation to inhibit the functions of FOXP2 isoforms including FOXP2Ex10+ lacking forkhead domain. Foxp2(R552H) knock-in mouse pups exhibit impaired ultrasonic vocalization and poor dendritic development in Purkinje cells. However, expressions of Foxp2 isoforms in the developing Purkinje are unclear. The appearance of 'apical cytoplasmic swelling' (mitochondria-rich regions that are the source of budding processes) correlates with dendritic development of Purkinje cells. In the present study, we focused on Foxp2 isoforms localizing to the apical cytoplasmic swelling and identified two isoforms lacking forkhead domain: Foxp2Ex12+ and Foxp2Ex15. They partly localized to the membrane fraction that includes mitochondria. Foxp2Ex12+ mainly localized to the apical cytoplasmic swelling in early developing Purkinje cells at the stellate stage (P2-P4). Mitochondrial localization of Foxp2Ex12+ in Purkinje cells was confirmed by immune-electron microscopic analysis. Foxp2Ex12+ may play a role in dendritic development in Purkinje cells.
authors: Center for Medical Science, International University of Health and Welfare, Otawara, Tochigi, Japan.
authors: Yuko
authors: Y
authors: Tanabe
authors: Yuji
authors: Y
authors: Fujiwara
authors: Ayumi
authors: A
authors: Matsuzaki
authors: Eriko
authors: E
authors: Fujita
authors: Tadashi
authors: T
authors: Kasahara
authors: Shigeki
authors: S
authors: Yuasa
authors: Takashi
authors: T
authors: Momoi
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000235:genetics; D064026:Calbindins; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development*; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D005333:Fetus; D051858:Forkhead Transcription Factors / Q000145:classification / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006639:Histidine / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D011689:Purkinje Cells / Q000648:ultrastructure*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D012097:Repressor Proteins / Q000145:classification / Q000235:genetics*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014465:Ultrasonics; D014828:Vocalization, Animal / Q000502:physiology; D000099052:CRF Receptor, Type 1
chemical_list: D064026:Calbindins; D051858:Forkhead Transcription Factors; C432918:Foxp2 protein, mouse; D020033:Protein Isoforms; D018019:Receptors, Corticotropin-Releasing Hormone; D012097:Repressor Proteins; D064030:S100 Calcium Binding Protein G; D006639:Histidine; D000099052:CRF Receptor, Type 1; D045304:Cytochromes c; D001120:Arginine