Institute of Neuroscience, Institute of Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403, USA.
Institute of Neuroscience, Institute of Molecular Biology, Howard Hughes Medical Institute, University of Oregon, Eugene, OR 97403, USA
Development. 2019 Apr 5;146(7):dev175570. doi: 10.1242/dev.175570.
The generation of neuronal diversity is essential for circuit formation and behavior. Morphological differences in sequentially born neurons could be due to intrinsic molecular identity specified by temporal transcription factors (henceforth called intrinsic temporal identity) or due to changing extrinsic cues. Here, we have used the NB7-1 lineage to address this issue. NB7-1 generates the U1-U5 motor neurons sequentially; each has a distinct intrinsic temporal identity due to inheritance of different temporal transcription factors at its time of birth. We show that the U1-U5 neurons project axons sequentially, followed by sequential dendrite extension. We misexpressed the earliest temporal transcription factor, Hunchback, to create 'ectopic' U1 neurons with an early intrinsic temporal identity but later birth-order. These ectopic U1 neurons have axon muscle targeting and dendrite neuropil targeting that are consistent with U1 intrinsic temporal identity, rather than with their time of birth or differentiation. We conclude that intrinsic temporal identity plays a major role in establishing both motor axon muscle targeting and dendritic arbor targeting, which are required for proper motor circuit development.
神经元多样性的产生对于回路形成和行为至关重要。顺序产生的神经元在形态上的差异可能是由于时间转录因子所规定的内在分子特征(以下简称内在时间特征),也可能是由于外在线索的变化。在这里,我们使用 NB7-1 谱系来解决这个问题。NB7-1 依次产生 U1-U5 运动神经元;由于在出生时继承了不同的时间转录因子,每个神经元都具有独特的内在时间特征。我们表明 U1-U5 神经元依次投射轴突,然后是顺序的树突延伸。我们过表达了最早的时间转录因子 Hunchback,以创建具有早期内在时间特征但出生时间较晚的“异位”U1 神经元。这些异位 U1 神经元的轴突肌肉靶向和树突神经丛靶向与 U1 的内在时间特征一致,而不是与它们的出生时间或分化时间一致。我们的结论是,内在时间特征在建立运动轴突肌肉靶向和树突分支靶向方面起着重要作用,这是正确的运动回路发育所必需的。