Retinoid acid specifies neuronal identity through graded expression of Ascl1.
Retinoid acid specifies neuronal identity through graded expression of Ascl1.
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DOI：
10.1016/j.cub.2013.01.046
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发表时间：
2013-03-04
期刊：
影响因子：
9.2
通讯作者：
Briscoe, James
中科院分区：
文献类型：
--
作者：
Jacob, John;Kong, Jennifer;Moore, Steven;Milton, Christopher;Sasai, Noriaki;Gonzalez-Quevedo, Rosa;Terriente, Javier;Imayoshi, Itaru;Kageyama, Ryoichoro;Wilkinson, David G.;Novitch, Bennett G.;Briscoe, James
神经管中的细胞多样性和组织依赖于沿沿着正交轴作用的外部信号的整合。这些被认为通过触发转录因子组合表达的全或无变化来指定不同的细胞身份。在共同的背腹信号，音刺猬，和不同的前-后（A-P）诱导信号的影响下，两个地形相关的祖细胞池，共享一个共同的转录代码产生的多巴胺能和V3神经元在后脑和脊髓，分别。这些神经元具有不同的生理特性、功能和连接性。神经精神疾病中的血清素能参与促使其有丝分裂后的命运决定因素，其中包括Gata 2，Lmx 1b和Pet 1，而V3神经元表达Sim 1的剧目更大的特点。不同的V3神经元和V4神经元的身份如何从共享共同转录密码的祖细胞中出现尚不清楚。在这里，我们表明，类维生素A活性的变化，在这两个祖池决定他们的命运。类维生素A通过Notch信号传导控制转录因子Ascl 1的祖细胞中的表达水平，Ascl 1以剂量依赖性方式选择多巴胺能和V3神经元身份。因此，转录密码的单个组分的表达的数量差异可以选择不同的细胞命运。神经管中Ascl 1的分级表达指定了不同的神经元亚型类视色素活性和Ascl 1表达呈负相关类视色素信号传导的二元差异通过Notch调节Ascl 1的分级表达Ascl 1的剂量依赖性效应解释了神经元亚型的区域分离
Cell diversity and organization in the neural tube depend on the integration of extrinsic signals acting along orthogonal axes. These are believed to specify distinct cellular identities by triggering all-or-none changes in expression of combinations of transcription factors. Under the influence of a common dorsoventral signal, sonic hedgehog, and distinct anterior-posterior (A-P) inductive signals, two topographically related progenitor pools that share a common transcriptional code produce serotonergic and V3 neurons in the hindbrain and spinal cord, respectively. These neurons have different physiological properties, functions, and connectivity. Serotonergic involvement in neuropsychiatric diseases has prompted greater characterization of their postmitotic repertoire of fate determinants, which include Gata2, Lmx1b, and Pet1, whereas V3 neurons express Sim1. How distinct serotonergic and V3 neuronal identities emerge from progenitors that share a common transcriptional code is not understood. Here, we show that changes in retinoid activity in these two progenitor pools determine their fates. Retinoids, via Notch signaling, control the expression level in progenitors of the transcription factor Ascl1, which selects serotonergic and V3 neuronal identities in a dose-dependent manner. Therefore, quantitative differences in the expression of a single component of a transcriptional code can select distinct cell fates. ► Graded Ascl1 expression in the neural tube specifies distinct neuronal subtypes ► Retinoid activity and Ascl1 expression are inversely correlated ► Binary differences in retinoid signaling regulate graded Ascl1 expression via Notch ► Dose-dependent effects of Ascl1 explains regional segregation of neuronal subtypes
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DOI：
10.1126/science.1205295
发表时间：
2011-07-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ray RS;Corcoran AE;Brust RD;Kim JC;Richerson GB;Nattie E;Dymecki SM
通讯作者：
Dymecki SM
影响因子：
64.5
作者：
Dasen, Jeremy S.;De Camilli, Alessandro;Jessell, Thomas M.
通讯作者：
Jessell, Thomas M.
影响因子：
4.6
作者：
Craven, SE;Lim, KC;Rosenthal, A
通讯作者：
Rosenthal, A
影响因子：
25
作者：
Pattyn, A;Simplicio, N;Brunet, JF
通讯作者：
Brunet, JF
影响因子：
10.5
作者：
Ribes, Vanessa;Balaskas, Nikolaos;Briscoe, James
通讯作者：
Briscoe, James