A novel post-developmental role of the Hox genes underlies normal adult behavior.
A novel post-developmental role of the Hox genes underlies normal adult behavior.
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DOI：
10.1073/pnas.2209531119
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发表时间：
2022-12-06
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
在发育结束时，细胞必须使指导其分化的遗传程序失活，并开启确保细胞稳定性和生理学的分子密码脚本。在神经系统内，虽然对基因如何影响神经发育过程有了实质性的了解，但成年有丝分裂后神经元中细胞功能和稳定性的遗传程序仍然很大程度上未知。在这里，我们调查这个问题在果蝇，并发现，Hox基因编码一个家庭的进化保守的发育调节，轴向模式的关键是必不可少的有丝分裂后的神经元和成年人的行为的正常生理。基于Hox基因的进化保守性，我们认为它们也可能在包括人类在内的其他物种的成年形式中发挥关键的神经生理作用。成熟神经元和神经回路稳定性的分子机制知之甚少。在这里，我们探讨这个问题，并发现Hox基因是遗传程序的一个组成部分，维持正常的神经功能在成年果蝇。我们发现，发育后下调的Hox基因Ultrabithorax（UBX）在成年神经元导致大量的异常飞行。绘制这些效应的细胞基础揭示了Ubx在多巴胺能神经元的一个子集中是必需的，并且结合光遗传学的细胞电路分析使我们能够将这些多巴胺能神经元与飞行控制联系起来。功能成像实验表明，Ubx是必要的正常多巴胺能活性，和神经元特异性RNA测序定义两个以前未表征的离子通道编码基因作为潜在的介质Ubx的行为作用。我们的研究揭示了Hox系统在控制成年人行为和神经功能中的新作用，基于Hox系统在远亲动物门中的广泛进化保守性，我们预测Hox基因可能在其他物种（包括人类）的成年形式中发挥神经生理学作用。
At the end of development, cells must deactivate the genetic programs that guided their differentiation and switch on the molecular code script that ensures cellular stability and physiology. Within the nervous system, while there is a substantial understanding of how genes influence neuro-developmental processes, the genetic programs underlying cell function and stability in adult post-mitotic neurons remain largely unknown. Here we investigate this problem in Drosophila and discover that the Hox genes—which encode a family of evolutionarily-conserved developmental regulators, key for axial patterning—are essential for the normal physiology of post-mitotic neurons and adult behavior. Based on the evolutionary conservation of the Hox genes, we suggest that they may also play key neurophysiological roles in the adult forms of other species, including humans. The molecular mechanisms underlying the stability of mature neurons and neural circuits are poorly understood. Here we explore this problem and discover that the Hox genes are a component of the genetic program that maintains normal neural function in adult Drosophila. We show that post-developmental downregulation of the Hox gene Ultrabithorax (Ubx) in adult neurons leads to substantial anomalies in flight. Mapping the cellular basis of these effects reveals that Ubx is required within a subset of dopaminergic neurons, and cell circuitry analyses in combination with optogenetics allow us to link these dopaminergic neurons to flight control. Functional imaging experiments show that Ubx is necessary for normal dopaminergic activity, and neuron-specific RNA-sequencing defines two previously uncharacterized ion channel-encoding genes as potential mediators of Ubx behavioral roles. Our study thus reveals a novel role of the Hox system in controlling adult behavior and neural function. Based on the broad evolutionary conservation of the Hox system across distantly related animal phyla, we predict that the Hox genes might play neurophysiological roles in adult forms of other species, including humans.
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DOI：
10.1093/bioinformatics/bts251
发表时间：
2012-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Jiao X;Sherman BT;Huang da W;Stephens R;Baseler MW;Lane HC;Lempicki RA
通讯作者：
Lempicki RA
影响因子：
3.5
作者：
Cassari, Marlene;Issa, Abdul-Raouf;Birman, Serge
通讯作者：
Birman, Serge
影响因子：
2.8
作者：
Bender, John A.;Dickinson, Michael H.
通讯作者：
Dickinson, Michael H.
影响因子：
5.3
作者：
Luan, HJ;Lemon, WC;White, BH
通讯作者：
White, BH
DOI：
10.1523/jneurosci.0081-21.2021
发表时间：
2021-10-06
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Klann M;Issa AR;Pinho S;Alonso CR
通讯作者：
Alonso CR