An evolutionarily acquired microRNA shapes development of mammalian cortical projections.
An evolutionarily acquired microRNA shapes development of mammalian cortical projections.
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一种进化获得的microRNA塑造了哺乳动物皮层投射的发育。
DOI：
10.1073/pnas.2006700117
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发表时间：
2020-11-17
影响因子：
11.1
通讯作者：
Tharin S
中科院分区：
文献类型：
--
作者：
Diaz JL;Siththanandan VB;Lu V;Gonzalez-Nava N;Pasquina L;MacDonald JL;Woodworth MB;Ozkan A;Nair R;He Z;Sahni V;Sarnow P;Palmer TD;Macklis JD;Tharin S
哺乳动物中枢神经系统包含来自大脑皮层的独特投射，被认为是支持复杂运动和认知技能，包括皮质脊髓束和胼胝体。产生这些投射的神经元--皮质脊髓和胼胝体投射神经元--从相同的祖细胞发育而来，但获得了截然不同的命运。控制皮质投射神经元命运的已知基因的广泛进化保守性提出了一个问题，即更保守的皮质脊髓和胼胝体投射是如何进化的。我们确定了一个选择性表达的microRNA簇皮质脊髓投射神经元和胎盘哺乳动物专用。其中一种microRNA通过调节胼胝体基因LMO 4促进皮质脊髓的命运，表明发育过程中microRNA的调节促进神经元多样性的进化的机制。皮质脊髓束是哺乳动物所特有的，胼胝体是胎盘哺乳动物（真兽目）所特有的。这些结构的出现被认为是复杂运动和认知技能进化获得的基础。皮质脊髓运动神经元（CSMN）和胼胝体投射神经元（CPN）分别是皮质脊髓束和胼胝体的原型投射神经元。尽管在脊椎动物中已经鉴定了许多CSMN和CPN发育的保守转录调节因子，但没有一个是哺乳动物特有的，并且大多数在多个投射神经元亚型中共表达。在这里，我们发现了17个富含CSMN的microRNA（miRNAs），其中15个映射到一个单一的基因组簇，这是专为真兽目。其中之一，miR-409- 3 p，促进CSMN亚型的身份，部分通过抑制LMO 4，CPN发展的关键转录调节因子。在体内，miR-409- 3 p足以将深层CPN转化为CSMN。这是真兽目动物进化获得的miRNA的证明，其改进了皮质投射神经元亚型的发育。我们的研究结果表明，miRNAs与真兽目动物神经元亚型和投射多样性的增加有关，这是它们复杂行为的解剖学基础。
The mammalian central nervous system contains unique projections from the cerebral cortex thought to underpin complex motor and cognitive skills, including the corticospinal tract and corpus callosum. The neurons giving rise to these projections—corticospinal and callosal projection neurons—develop from the same progenitors, but acquire strikingly different fates. The broad evolutionary conservation of known genes controlling cortical projection neuron fates raises the question of how the more narrowly conserved corticospinal and callosal projections evolved. We identify a microRNA cluster selectively expressed by corticospinal projection neurons and exclusive to placental mammals. One of these microRNAs promotes corticospinal fate via regulation of the callosal gene LMO4, suggesting a mechanism whereby microRNA regulation during development promotes evolution of neuronal diversity. The corticospinal tract is unique to mammals and the corpus callosum is unique to placental mammals (eutherians). The emergence of these structures is thought to underpin the evolutionary acquisition of complex motor and cognitive skills. Corticospinal motor neurons (CSMN) and callosal projection neurons (CPN) are the archetypal projection neurons of the corticospinal tract and corpus callosum, respectively. Although a number of conserved transcriptional regulators of CSMN and CPN development have been identified in vertebrates, none are unique to mammals and most are coexpressed across multiple projection neuron subtypes. Here, we discover 17 CSMN-enriched microRNAs (miRNAs), 15 of which map to a single genomic cluster that is exclusive to eutherians. One of these, miR-409-3p, promotes CSMN subtype identity in part via repression of LMO4, a key transcriptional regulator of CPN development. In vivo, miR-409-3p is sufficient to convert deep-layer CPN into CSMN. This is a demonstration of an evolutionarily acquired miRNA in eutherians that refines cortical projection neuron subtype development. Our findings implicate miRNAs in the eutherians’ increase in neuronal subtype and projection diversity, the anatomic underpinnings of their complex behavior.
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影响因子：
8.8
作者：
Bian S;Hong J;Li Q;Schebelle L;Pollock A;Knauss JL;Garg V;Sun T
通讯作者：
Sun T
影响因子：
3.4
作者：
Chen Y;Bian S;Zhang J;Zhang H;Tang B;Sun T
通讯作者：
Sun T
DOI：
10.1073/pnas.0509032102
发表时间：
2005-12-06
影响因子：
11.1
作者：
Chen, JG;Rasin, MR;Sestan, N
通讯作者：
Sestan, N
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y