Organization of Purkinje cell development by neuronal MEGF11 in cerebellar granule cells
Soyoung Jun,
Muwoong Kim,
Heeyoun Park,
Eunmi Hwang,
Yukio Yamamoto,
Keiko Tanaka-Yamamoto
Affiliations
Soyoung Jun
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea
Muwoong Kim
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea
Heeyoun Park
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
Eunmi Hwang
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea
Yukio Yamamoto
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Corresponding author
Keiko Tanaka-Yamamoto
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea; Corresponding author
Summary: As cerebellar granule cells (GCs) coordinate the formation of regular cerebellar networks during postnatal development, molecules in GCs are expected to be involved. Here, we test the effects of the knockdown (KD) of multiple epidermal growth factor-like domains protein 11 (MEGF11), which is a homolog of proteins mediating astrocytic phagocytosis but is substantially increased at the later developmental stages of GCs on cerebellar development. MEGF11-KD in GCs of developing mice results in abnormal cerebellar structures, including extensively ectopic Purkinje cell (PC) somas, and in impaired motor functions. MEGF11-KD also causes abnormally asynchronous synaptic release from GC axons, parallel fibers, before the appearance of abnormal cerebellar structures. Interestingly, blockade of this abnormal synaptic release restores most of the cerebellar structures. Thus, apart from phagocytic functions of its related homologs in astrocytes, MEGF11 in GCs promotes proper PC development and cerebellar network formation by regulating immature synaptic transmission.
