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TrkB-dependent EphrinA reverse signaling regulates callosal axonfasciculate growth downstream of Neurod2/6В журнале Cerebral Cortex опубликована статья TrkB-dependent EphrinA reverse signaling regulates callosal axonfasciculate growth downstream of Neurod2/6, в группе авторов из Institute of Cell Biology and Neurobiology (Charité Universitätsmedizin Berlin,D-10117,Berlin,Germany) и Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod (603950, NizhnyNovgorodOblast, Russia) В. С. Тарабыкин - сотрудник лаборатории онтогенетики НИИ медицинской генетики Томского НИМЦ.
Abnormal development of corpus callosum is relatively common and causes a broad spectrum of cognitive impairments in humans. We use acallosal Neurod2/6-deficient mice to study callosal axon guidance within the ipsilateral cerebral cortex. Initial callosal tracts form but fail to traverse the ipsilateral cingulum and are not attracted towards the midline in the absence of Neurod2/6. We show that the restoration of Ephrin-A4 (EfnA4) expression in the embryonic neocortex of Neurod2/6-deficient embryos is sufficient to partially rescue targeted callosal axon growth towards the midline. EfnA4 cannot directly mediate reverse signaling within outgrowing axons, but it forms co-receptor complexes with TrkB (Ntrk2). The ability of EfnA4 to rescue the guided growth of a subset of callosal axons in Neurod2/6-deficient mice is abolished by the co-expression of dominant negative TrkBK571N (kinase-dead) or TrkBY515F (SHC-binding deficient) variants, but not by TrkBY816F (PLCγ1-binding deficient). Additionally, EphA4 is repulsive to EfnA4-positive medially projecting axons in organotypic brain slice culture. Collectively, we suggest that EfnA4-mediated reverse signaling acts via TrkB-SHC and is required for ipsilateral callosal axon growth accuracy towards the midline downstream of Neurod family factors.
Kuo Yan, Ingo Bormuth, Olga Bormuth, Svetlana Tutukova, Ana Renner, Paraskevi Bessa, Theres Schaub, Marta Rosário, Victor Tarabykin. TrkB-dependent EphrinA reverse signaling regulates callosal axonfasciculate growth downstream of Neurod2/6 // Cerebral Cortex, 2022, 1–16 DOI: 10.1093/cercor/bhac170 Cсылка на источник информации: https://doi.org/10.1093/cercor/bhac170
просмотров: 1184, опубликовано: 22.06.2022
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