miR-409-3p represses Cited2 to refine neocortical layer V projection neuron identity.
miR-409-3p represses Cited2 to refine neocortical layer V projection neuron identity.
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DOI：
10.3389/fnins.2022.931333
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发表时间：
2022
影响因子：
4.3
通讯作者：
Tharin, Suzanne
中科院分区：
文献类型：
--
作者：
Wagner, Nikolaus R.;Sinha, Ashis;Siththanandan, Verl;Kowalchuk, Angelica M.;MacDonald, Jessica L.;Tharin, Suzanne
关键词：
皮质脊髓束和胼胝体的进化被认为是哺乳动物复杂运动和认知能力扩展的基础。轴突构成这些束的神经元，即皮质脊髓和胼胝体投射神经元，其调控发育的分子机制尚不完全清楚。我们之前的工作发现了一个microRNAs基因组簇，mirna /12qF1，它是胎盘哺乳动物独有的，在发育过程中由皮质脊髓神经元特异性表达，而在胼胝体投射神经元中被排除。我们发现其中一种miR-409-3p可以将V层胼胝体转化为皮质脊髓投射神经元，部分通过抑制转录调节因子Lmo4发挥作用。在这里，我们发现miR-409-3p也直接抑制转录共调节因子Cited2，后者在神经发生的最早阶段就在胼胝体投射神经元中高度表达。Cited2在胚胎新皮层的中间祖细胞（IPCs）中高度表达，而编码miR-409-3p的Mirg在这些祖细胞中被排除在外。IPCs中miR-409-3p功能获得（GOF）导致已建立的Cited2功能丧失（LOF）的表型。在发育后期，miR-409-3p GOF和Cited2 LOF都以牺牲v层胼胝体投射神经元标记物为代价促进皮质脊髓的表达。综上所述，这项工作确定了先前描述的miR-409-3p在控制IPC数量和Cited2在控制胼胝体命运中的作用。因此，miR-409-3p可能与其他Mirg/12qF1 mirna合作，抑制Cited2作为V层内神经元细胞命运细化的多方面调控的一部分，结合了祖细胞和有丝分裂后神经元的多个水平的分子调控。
The evolutionary emergence of the corticospinal tract and corpus callosum are thought to underpin the expansion of complex motor and cognitive abilities in mammals. Molecular mechanisms regulating development of the neurons whose axons comprise these tracts, the corticospinal and callosal projection neurons, remain incompletely understood. Our previous work identified a genomic cluster of microRNAs (miRNAs), Mirg/12qF1, that is unique to placental mammals and specifically expressed by corticospinal neurons, and excluded from callosal projection neurons, during development. We found that one of these, miR-409-3p, can convert layer V callosal into corticospinal projection neurons, acting in part through repression of the transcriptional regulator Lmo4. Here we show that miR-409-3p also directly represses the transcriptional co-regulator Cited2, which is highly expressed by callosal projection neurons from the earliest stages of neurogenesis. Cited2 is highly expressed by intermediate progenitor cells (IPCs) in the embryonic neocortex while Mirg, which encodes miR-409-3p, is excluded from these progenitors. miR-409-3p gain-of-function (GOF) in IPCs results in a phenocopy of established Cited2 loss-of-function (LOF). At later developmental stages, both miR-409-3p GOF and Cited2 LOF promote the expression of corticospinal at the expense of callosal projection neuron markers in layer V. Taken together, this work identifies previously undescribed roles for miR-409-3p in controlling IPC numbers and for Cited2 in controlling callosal fate. Thus, miR-409-3p, possibly in cooperation with other Mirg/12qF1 miRNAs, represses Cited2 as part of the multifaceted regulation of the refinement of neuronal cell fate within layer V, combining molecular regulation at multiple levels in both progenitors and post-mitotic neurons.
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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
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C
影响因子：
16.2
作者：
Alcamo, Elizabeth A.;Chirivella, Laura;McConnell, Susan K.
通讯作者：
McConnell, Susan K.
DOI：
10.1073/pnas.2006700117
发表时间：
2020-11-17
影响因子：
11.1
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
通讯作者：
Tharin S