Retrograde semaphorin signaling regulates synapse elimination in the developing mouse brain.
Neural circuits are shaped by elimination of early-formed redundant synapses during postnatal development. Retrograde signaling from postsynaptic cells regulates synapse elimination. In this work, we identified semaphorins, a family of versatile cell recognition molecules, as retrograde signals for elimination of redundant climbing fiber to Purkinje cell synapses in developing mouse cerebellum. Knockdown of Sema3A, a secreted semaphorin, in Purkinje cells or its receptor in climbing fibers accelerated synapse elimination during postnatal day 8 (P8) to P18. Conversely, knockdown of Sema7A, a membrane-anchored semaphorin, in Purkinje cells or either of its two receptors in climbing fibers impaired synapse elimination after P15. The effect of Sema7A involves signaling by metabotropic glutamate receptor 1, a canonical pathway for climbing fiber synapse elimination. These findings define how semaphorins retrogradely regulate multiple processes of synapse elimination.
Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Naofumi
N
Uesaka
Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Motokazu
M
Uchigashima
Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Takayasu
T
Mikuni
Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Takanobu
T
Nakazawa
Laboratory of Animal Resources, Center for Disease Biology and Integrated Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Harumi
H
Nakao
Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
Hirokazu
H
Hirai
Laboratory of Animal Resources, Center for Disease Biology and Integrated Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Atsu
A
Aiba
Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Masahiko
M
Watanabe
Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. mkano-tky@m.u-tokyo.ac.jp.
Masanobu
M
Kano
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D011689:Purkinje Cells / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism*; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013569:Synapses / Q000235:genetics / Q000502:physiology*
D015703:Antigens, CD; D018094:Receptors, Metabotropic Glutamate; C488217:Sema3a protein, mouse; C485571:Sema7a protein, mouse; D040121:Semaphorin-3A; D039961:Semaphorins; C104077:metabotropic glutamate receptor type 1