Fmrp regulates neuronal balance in embryonic motor circuit formation.
Fmrp regulates neuronal balance in embryonic motor circuit formation.
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DOI：
10.3389/fnins.2022.962901
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发表时间：
2022
影响因子：
4.3
通讯作者：
Doll, Caleb A.
中科院分区：
文献类型：
--
作者：
Barker, Chase M.;Miles, Kaleb D.;Doll, Caleb A.
关键词：
运动行为需要各种神经细胞类型的平衡生产和整合。运动神经元位于脊髓中的离散位置，以特定肌肉为目标来驱动运动性收缩。专门的脊髓中间神经元调节和同步运动神经元活动，以实现协调的运动输出。脊髓中间神经元的比例和连通性的变化可以通过将抑制和兴奋的平衡倾斜到目标运动神经元上来彻底改变运动输出。重要的是，患有脆性X综合征（FXS）和相关自闭症谱系障碍的个体通常具有显著的运动挑战，包括重复行为和癫痫。FXS源于基因脆性X信使核糖核蛋白1（FMR 1）的转录沉默，该基因编码一种RNA结合蛋白，该蛋白涉及许多关键的神经发育过程，包括细胞特化。我们的工作表明，FMRP调节特定的中间神经元和运动神经元，包括早期胚胎运动电路的形成。我们发现，斑马鱼fmr1突变体产生盈余腹侧降（VeLD）中间神经元，一个早期出生的细胞来自运动神经元祖域（pMN）。由于VeLD中间神经元被假设为驱动最早自发运动的中央模式发生器，这种不平衡可能影响驱动运动的运动回路的形成和长期功能。fmr1胚胎还显示与抑制性突触相关的蛋白质表达减少，包括突触前转运蛋白vGAT和突触后支架Gephyrin。综上所述，我们发现fmr1突变体中胚胎运动回路形成的变化可能是持续性超兴奋的基础。
Motor behavior requires the balanced production and integration of a variety of neural cell types. Motor neurons are positioned in discrete locations in the spinal cord, targeting specific muscles to drive locomotive contractions. Specialized spinal interneurons modulate and synchronize motor neuron activity to achieve coordinated motor output. Changes in the ratios and connectivity of spinal interneurons could drastically alter motor output by tipping the balance of inhibition and excitation onto target motor neurons. Importantly, individuals with Fragile X syndrome (FXS) and associated autism spectrum disorders often have significant motor challenges, including repetitive behaviors and epilepsy. FXS stems from the transcriptional silencing of the gene Fragile X Messenger Ribonucleoprotein 1 (FMR1), which encodes an RNA binding protein that is implicated in a multitude of crucial neurodevelopmental processes, including cell specification. Our work shows that Fmrp regulates the formation of specific interneurons and motor neurons that comprise early embryonic motor circuits. We find that zebrafish fmr1 mutants generate surplus ventral lateral descending (VeLD) interneurons, an early-born cell derived from the motor neuron progenitor domain (pMN). As VeLD interneurons are hypothesized to act as central pattern generators driving the earliest spontaneous movements, this imbalance could influence the formation and long-term function of motor circuits driving locomotion. fmr1 embryos also show reduced expression of proteins associated with inhibitory synapses, including the presynaptic transporter vGAT and the postsynaptic scaffold Gephyrin. Taken together, we show changes in embryonic motor circuit formation in fmr1 mutants that could underlie persistent hyperexcitability.
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影响因子：
16.2
作者：
Dani, Adish;Huang, Bo;Bergan, Joseph;Dulac, Catherine;Zhuang, Xiaowei
通讯作者：
Zhuang, Xiaowei
影响因子：
4.3
作者：
Andrzejczuk LA;Banerjee S;England SJ;Voufo C;Kamara K;Lewis KE
通讯作者：
Lewis KE
DOI：
10.1016/j.ijdevneu.2015.02.004
发表时间：
2015-05-01
影响因子：
1.8
作者：
Bonaccorso, C. M.;Spatuzza, M.;Catania, M. V.
通讯作者：
Catania, M. V.
影响因子：
3.4
作者：
Fantuzzo, J. A.;Mirabella, V. R.;Pang, Z. P.
通讯作者：
Pang, Z. P.
影响因子：
2.5
作者：
El Idrissi, A;Ding, XH;Dobkin, C
通讯作者：
Dobkin, C