Pollington Heather Q, Doe Chris Q
Institute of Neuroscience, Howard Hughes Medical Institute, University of Oregon, Eugene, Oregon, United States of America.
PLoS Biol. 2025 Mar 31;23(3):e3002881. doi: 10.1371/journal.pbio.3002881. eCollection 2025 Mar.
Interneuron diversity within the central nervous system (CNS) is essential for proper circuit assembly. Functional interneurons must integrate multiple features, including combinatorial transcription factor (TF) expression, axon/dendrite morphology, and connectivity to properly specify interneuronal identity. Yet, how these different interneuron properties are coordinately regulated remains unclear. Here we used the Drosophila neural progenitor, NB5-2, known to generate late-born interneurons in a proprioceptive circuit, to determine if the early-born temporal transcription factor (TTF), Hunchback (Hb), specifies early-born interneuron identity, including molecular profile, axon/dendrite morphology, presynapse targeting, and behavior. We found that prolonged Hb expression in NB5-2 increases the number of neurons expressing early-born TFs (Nervy, Nkx6, and Dbx) at the expense of late-born TFs (Runt and Zfh2); thus, Hb is sufficient to promote interneuron molecular identity. Hb is also sufficient to transform late-born neuronal morphology to early-born neuronal morphology. Furthermore, prolonged Hb promotes the relocation of late-born neuronal presynapses to early-born neuronal presynapse neuropil locations, consistent with a change in interneuron connectivity. Finally, we found that prolonged Hb expression led to defects in proprioceptive behavior, consistent with a failure to properly specify late-born interneurons in the proprioceptive circuit. We conclude that the Hb TTF is sufficient to specify multiple aspects of early-born interneuron identity, as well as disrupt late-born proprioceptive neuron function.
中枢神经系统（CNS）内中间神经元的多样性对于正确的神经回路组装至关重要。功能性中间神经元必须整合多种特征，包括组合转录因子（TF）表达、轴突/树突形态以及连接性，以正确确定中间神经元的身份。然而，这些不同的中间神经元特性是如何协同调节的仍不清楚。在这里，我们使用果蝇神经祖细胞NB5-2，已知它在本体感觉回路中产生晚期出生的中间神经元，来确定早期出生的时间转录因子（TTF）驼背蛋白（Hb）是否能确定早期出生的中间神经元身份，包括分子特征、轴突/树突形态、突触前靶向和行为。我们发现，NB5-2中Hb表达的延长会增加表达早期出生TFs（Nervy、Nkx6和Dbx）的神经元数量，同时以晚期出生TFs（Runt和Zfh2）为代价；因此，Hb足以促进中间神经元的分子身份。Hb也足以将晚期出生的神经元形态转变为早期出生的神经元形态。此外，延长的Hb促进晚期出生的神经元突触前向早期出生的神经元突触前神经纤维网位置的重新定位，这与中间神经元连接性的变化一致。最后，我们发现延长的Hb表达导致本体感觉行为缺陷，这与在本体感觉回路中未能正确确定晚期出生的中间神经元一致。我们得出结论，Hb TTF足以确定早期出生的中间神经元身份的多个方面，以及破坏晚期出生的本体感觉神经元功能。
