Peripheral nerve development in zebrafish requires muscle patterning by tcf15/paraxis
Peripheral nerve development in zebrafish requires muscle patterning by tcf15/paraxis
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DOI：
10.1016/j.ydbio.2022.07.001
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发表时间：
2022-07-18
影响因子：
2.7
通讯作者：
Petersen，Sarah C.
中科院分区：
文献类型：
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作者：
Limbach，Lauren E.;Penick，Rocky L.;Petersen，Sarah C.
脊椎动物的周围神经系统(PNS)是一个复杂的网络，它在全身传递感觉和运动信息。在发育过程中，细胞外信号引导轴突和神经胶质细胞在周围组织中迁移。目前，支配三叉神经节轴突-神经胶质细胞模式的一系列分子还不完全清楚。为了阐明对周围神经发育至关重要的因素，我们对新的斑马鱼突变体stl159进行了表征，该突变体在三叉神经核模式中表现出异常。在这些突变体中，与轴肌相邻发育的运动神经和感觉神经无法正常伸展，后侧线系统中的神经肥大以及神经脊源性黑素细胞的位置错误。L159基因损伤位于基本螺旋-环-螺旋转录因子tcf15中，该因子先前已被认为与轴肌的正常发育有关。我们发现，通过CRISPR-Cas9基因组编辑靶向缺失tCF15导致观察到159个突变体的PNS模式异常。由于cf15在神经延伸之前在发育中的肌肉中表达，而不是在神经元或神经胶质细胞中表达，我们预测atcf15非细胞自主地通过调节细胞外模式信号促进斑马鱼周围神经模式的形成。我们的工作强调了肌肉衍生因子在三叉神经节发育中的重要性。
The vertebrate peripheral nervous system (PNS) is an intricate network that conveys sensory and motor information throughout the body. During development, extracellular cues direct the migration of axons and glia through peripheral tissues. Currently, the suite of molecules that govern PNS axon-glial patterning is incompletely understood. To elucidate factors that are critical for peripheral nerve development, we characterized the novel zebrafish mutant,stl159, that exhibits abnormalities in PNS patterning. In these mutants, motor and sensory nerves that develop adjacent to axial muscle fail to extend normally, and neuromasts in the posterior lateral line system, as well as neural crest-derived melanocytes, are incorrectly positioned. Thestl159genetic lesion lies in the basic helix-loop-helix (bHLH) transcription factortcf15, which has been previously implicated in proper development of axial muscles. We find that targeted loss oftcf15via CRISPR-Cas9 genome editing results in the PNS patterning abnormalities observed instl159mutants. Becausetcf15is expressed in developing muscle prior to nerve extension, rather than in neurons or glia, we predict thattcf15non-cell-autonomously promotes peripheral nerve patterning in zebrafish through regulation of extracellular patterning cues. Our work underscores the importance of muscle-derived factors in PNS development.