Neural tube patterning by Krox20 and emergence of a respiratory control

Neural tube patterning by Krox20 and emergence of a respiratory control
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DOI:
10.1016/j.resp.2005.02.014
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发表时间:
2005-11-15
影响因子:
2.3
通讯作者:
Fortin, G
Fortin, G
中科院分区:
医学4区
文献类型:
--
作者:
Borday, C;Chatonnet, F;Fortin, G

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最近的数据开始弥合控制后脑神经管区域模式的发育事件与胎儿呼吸行为的出现及其出生后至关重要的适应功能之间的差距。在脊椎动物中,HOX并列基因和HOX调节基因以一种保守的方式协调后脑-菱形脑发育区块的瞬时形成,在此过程中脑干的节律性神经元网络发展。在小鼠中,这些基因中的一些基因的遗传失活会导致出生时的病理性呼吸,这表明菱形3和4衍生区域对于维持呼吸频率至关重要。在胚胎7天的鸡胚中,我们研究了在胚胎1.5天分离的菱形核组合所产生的神经管岛上产生的神经元活动。使用功能增益方法,我们揭示了转录因子Krox20在诱导后脑副面部水平的节律生成器中的作用,该转录因子指定了菱形核3和5。发育基因的选择和对中枢神经系统前体细胞命运的区域协调可能为神经元网络形成和功能的保守方面提供进一步的线索。然而,最直接的问题是利用后脑早期产生的节律活动来追求它们下游的细胞和分子靶标,因为似乎很可能就是在这里,生理性的特性最终将在出生时发挥关键作用。(C)2005 Elsevier B.V.保留所有权利。
Recent data begin to bridge the gap between developmental events controlling hindbrain neural tube regional patterning and the emergence of breathing behaviour in the fetus and its vital adaptive function after birth. In vertebrates, Hox paralogs and Hox-regulating genes orchestrate, in a conserved manner, the transient formation of developmental compartments in the hindbrain, the rhombomeres, in which rhythmic neuronal networks of the brainstem develop. Genetic inactivation of some of these genes in mice leads to pathological breathing at birth pointing to the vital importance of rhombomere 3 and 4 derived territories for maintenance of the breathing frequency. In chick embryo at E7, we investigated neuronal activities generated in neural tube islands deriving from combinations of rhombomeres isolated at embryonic day E1.5. Using a gain of function approach, we reveal a role of the transcription factor Krox20, specifying rhombomeres 3 and 5, in inducing a rhythm generator at the parafacial level of the hindbrain. The developmental genes selecting and regionally coordinating the fate of CNS progenitors may hold further clues to conserved aspects of neuronal network formation and function. However, the most immediate concern is to take advantage of early generated rhythmic activities in the hindbrain to pursue their downstream cellular and molecular targets, for it seems likely that it will be here that rhythmogenic properties will eventually take on a vital role at birth. (c) 2005 Elsevier B.V. All rights reserved.