Distinct FGFs promote differentiation of excitatory and inhibitory synapses.
Distinct FGFs promote differentiation of excitatory and inhibitory synapses.
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作者：
The differential formation of excitatory (glutamatergic) and inhibitory (GABAergic) synapses is a critical step for the proper functioning of the brain. Their imbalance may lead to various neurological disorders such as autism, schizophrenia, Tourette syndrome and epilepsy. Synapses are formed through the communication between the appropriate synaptic partners. However, the molecular mechanisms that mediate the formation of specific synaptic types are not known. Here we show that two members of the fibroblast growth factor (FGF) family, FGF22 and FGF7, promote the organization of excitatory and inhibitory presynaptic terminals, respectively, as target-derived presynaptic organizers. FGF22 and FGF7 are expressed by CA3 pyramidal neurons in the hippocampus. The differentiation of excitatory or inhibitory nerve terminals on dendrites of CA3 pyramidal neurons is specifically impaired in mutants lacking FGF22 or FGF7. These presynaptic defects are rescued by postsynaptic expression of the appropriate FGF. FGF22-deficient mice are resistant and FGF7-deficient mice are prone to epileptic seizures, as expected from the alterations in excitatory/inhibitory balance. Differential effects by FGF22 and FGF7 involve both their distinct synaptic localizations and use of different signaling pathways. These results demonstrate that specific FGFs act as target-derived presynaptic organizers and help organize specific presynaptic terminals in the mammalian brain.
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影响因子：
64.8
作者：
Lin, Yingxi;Bloodgood, Brenda L.;Hauser, Jessica L.;Lapan, Ariya D.;Koon, Alex C.;Kim, Tae-Kyung;Hu, Linda S.;Malik, Athar N.;Greenberg, Michael E.
通讯作者：
Greenberg, Michael E.
影响因子：
4.8
作者：
Umemori, Hisashi;Sanes, Joshua R.
通讯作者：
Sanes, Joshua R.
影响因子：
2.9
作者：
GONZALEZ, AM;BERRY, M;BAIRD, A
通讯作者：
BAIRD, A
影响因子：
3.5
作者：
Xiao, Maolei;Xu, Lin;Ornitz, David M.
通讯作者：
Ornitz, David M.
影响因子：
1.7
作者：
Singer, HS;Minzer, K
通讯作者：
Minzer, K