![]() ![]() These neurites stochastically retract and elongate for a period of hours to days before a single neurite is specified as the axon ( Figure 1a). The next challenge is to understand how different signals select the “winning axon”.ĭuring development, hippocampal neurons transit through a multi-polar intermediate state in which neurons typically extend 4–5 immature neurites, which are each capable of becoming either an axon or a dendrite ( Barnes and Polleux, 2009 Dotti et al., 1988). This would allow each projection to explore its environment in the search for signals that promote axon growth. Winans et al.’s findings suggest that actin waves direct axon-promoting proteins to axons and promote competition between the projections early on by generating random fluctuations that allow all the projections to grow and retract. This work shows that actin waves make the projections wider to create space for more microtubules to form, which increases the transport of axon-promoting proteins to the projections. Furthermore, the actin waves promote the formation of more microtubule filaments. When a wave of actin reaches a projection, the projection grows for a while and then stops until the next actin wave arrives. The experiments show that a protein called actin forms a mesh of filaments in a wave-like manner, starting in the cell body and moving outwards into the projections. used microscopy to study the transport of axon-promoting proteins in hippocampal neurons. However, it is not clear what drives these fluctuations. In immature neurons, kinesin motors randomly move in and out of different projections, before settling in the projection that will grow into the axon. These axon-promoting proteins are carried to the axons by a motor protein called kinesin, which moves along fibers called microtubules. It is believed that signal proteins inside the neuron that promote the formation of an axon selectively accumulate in a projection as it grows into an axon. These projections randomly retract and lengthen for a while before a single projection grows into an axon and the others become dendrites. In the early stages of development, an immature neuron sends out multiple projections that extend out in all directions from its cell body. ![]() In animal embryos, immature neurons in part of the brain called the hippocampus – which is crucial for learning and forming memories – develop into mature neurons through a series of steps. Signals are received by branch-like projections called dendrites, pass through the cell body and then pass along a long projection called the axon before being transmitted to the dendrites of neighboring neurons. ![]() Nerve cells (also known as neurons) connect with each other to form complex networks through which signals are carried around the body. We propose that actin waves create large stochastic fluctuations in microtubule-based transport and neurite outgrowth, promoting competition between neurites as they explore the environment until sufficient external cues can direct one to become the axon. Actin waves also require microtubule polymerization, arguing that positive feedback links these two components. Our data argue for a mechanical control system whereby actin waves transiently widen the neurite shaft to allow increased microtubule polymerization to direct Kinesin-based transport and create bursts of neurite extension. We show that actin waves, which stochastically migrate from the cell body towards neurite tips, direct microtubule-based transport during the multi-polar state. Hallmarks of the multi-polar state are large fluctuations in microtubule-based transport into and outgrowth of different neurites, although what drives these fluctuations remains elusive. Many developing neurons transition through a multi-polar state with many competing neurites before assuming a unipolar state with one axon and multiple dendrites.
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