Serial synapse formation through filopodial competition for synaptic seeding factors
Serial synapse formation through filopodial competition for synaptic seeding factors
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DOI：
10.1101/506378
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发表时间：
2018-12
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通讯作者：
M. N. Özel;Abhishek Kulkarni;Amr Hasan;Josephine Brummer;Marian Moldenhauer;Ilsa-Maria Daumann;Heike Wolfenberg;V. J. Dercksen;Ferdi Ridvan Kiral;Martin Weiser;S. Prohaska;M. von Kleist;P. Hiesinger
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文献类型：
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作者：
M. N. Özel;Abhishek Kulkarni;Amr Hasan;Josephine Brummer;Marian Moldenhauer;Ilsa-Maria Daumann;Heike Wolfenberg;V. J. Dercksen;Ferdi Ridvan Kiral;Martin Weiser;S. Prohaska;M. von Kleist;P. Hiesinger
在轴突寻路之后，生长锥从随机的丝状面探索过渡到有限数量突触的形成。丝状伪足和突触的相互作用如何确保大脑中强健的连通性仍然是一个具有挑战性的问题。在这里，我们开发了一种新的丝状动力学的4D分析方法和一个数据驱动的果蝇大脑R7光感受器轴突突触形成的计算模型。我们的实时数据支持“连续突触形成”模型，在任何时间点，只有单个“突触原性”丝状伪足通过竞争突触种子因子抑制其他丝状伪足的突触能力。突触种子因子Syd-1和Liprin-α的缺失导致这种抑制作用的丧失，丝状不稳定和突触形成减少，这足以导致整个轴突末端的不稳定。我们的模型提供了一种丝状的“赢者通吃”机制，确保形成适当数量的突触。
Following axon pathfinding, growth cones transition from stochastic filopodial exploration to the formation of a limited number of synapses. How the interplay of filopodia and synapse assembly ensures robust connectivity in the brain has remained a challenging problem. Here, we developed a new 4D analysis method for filopodial dynamics and a data-driven computational model of synapse formation for R7 photoreceptor axons in developing Drosophila brains. Our live data support a ‘serial synapse formation’ model, where at any time point only a single ‘synaptogenic’ filopodium suppresses the synaptic competence of other filopodia through competition for synaptic seeding factors. Loss of the synaptic seeding factors Syd-1 and Liprin-α leads to a loss of this suppression, filopodial destabilization and reduced synapse formation, which is sufficient to cause the destabilization of entire axon terminals. Our model provides a filopodial ‘winner-takes-all’ mechanism that ensures the formation of an appropriate number of synapses.