Early Commissural Diencephalic Neurons Control Habenular Axon Extension and Targeting
Early Commissural Diencephalic Neurons Control Habenular Axon Extension and Targeting
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DOI：
10.1016/j.cub.2016.11.038
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发表时间：
2017-01-23
期刊：
影响因子：
9.2
通讯作者：
Carl, Matthias
中科院分区：
文献类型：
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作者：
Beretta, Carlo A.;Dross, Nicolas;Carl, Matthias
大多数神经元群体形成于大脑的左侧和右侧。它们的传出轴突似乎沿着两侧沿着相似的通路同步生长，尽管两个半球之间的神经元或其环境通常不同[1-4]。如何控制这种协调很少受到关注。通常，神经元建立半球间连接，其可以用于整合大脑半球之间的信息（例如，[5]）。这种连合形成非常早，表明它们在胚胎发育期间协调同侧轴突导航的潜在发育作用[4]。为了解决双侧轴突生长的时空控制问题，我们应用长期延时成像来可视化发育中的斑马鱼胚胎中保守的左右不对称缰神经回路的形成[6]。虽然缰神经元在大脑半球的不同时间出生[7]，但我们发现缰轴突的伸长是同步发生的。轴突延伸的起始不是在缰网络本身内控制的，而是通过早期发育的近端间脑网络控制的。这个网络的连合神经元影响缰轴突同侧和对侧。它们的单侧缺失会损害连合的形成和协调的缰轴突伸长，并导致它们随后在大脑两侧的停滞。因此，缰神经回路的形成取决于第二个交叉连合网络，这有利于同侧投射缰轴突所需的半球之间的信息交换。这种网络形成的机制很可能适用于其他电路，只是由于技术限制而尚未被发现。
Most neuronal populations form on both the left and right sides of the brain. Their efferent axons appear to grow synchronously along similar pathways on each side, although the neurons or their environment often differ between the two hemispheres [1-4]. How this coordination is controlled has received little attention. Frequently, neurons establish interhemispheric connections, which can function to integrate information between brain hemispheres (e.g., [5]). Such commissures form very early, suggesting their potential developmental role in coordinating ipsilateral axon navigation during embryonic development [4]. To address the temporal-spatial control of bilateral axon growth, we applied long-term time-lapse imaging to visualize the formation of the conserved left-right asymmetric habenular neural circuit in the developing zebrafish embryo [6]. Although habenular neurons are born at different times across brain hemispheres [7], we found that elongation of habenular axons occurs synchronously. The initiation of axon extension is not controlled within the habenular network itself but through an early developing proximal diencephalic network. The commissural neurons of this network influence habenular axons both ipsilaterally and contralaterally. Their unilateral absence impairs commissure formation and coordinated habenular axon elongation and causes their subsequent arrest on both sides of the brain. Thus, habenular neural circuit formation depends on a second intersecting commissural network, which facilitates the exchange of information between hemispheres required for ipsilaterally projecting habenular axons. This mechanism of network formation may well apply to other circuits, and has only remained undiscovered due to technical limitations.