Teashirt 3 Regulates Development of Neurons Involved in Both Respiratory Rhythm and Airflow Control
Teashirt 3 Regulates Development of Neurons Involved in Both Respiratory Rhythm and Airflow Control
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DOI：
10.1523/jneurosci.1765-10.2010
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发表时间：
2010-07-14
影响因子：
5.3
通讯作者：
Fasano, Laurent
中科院分区：
文献类型：
--
作者：
Caubit, Xavier;Thoby-Brisson, Muriel;Fasano, Laurent
哺乳动物的新生儿呼吸涉及多个神经回路，但其遗传基础仍不清楚。缺乏锌指蛋白Teashirt 3（TSHZ 3）的小鼠无法呼吸，出生时死亡。Tshz 3在脑干参与呼吸的多个区域中表达，包括前Botzinger复合体（preBotC），胚胎面旁呼吸组（e-pF）和控制上呼吸道的颅运动神经元。Tshz 3失活导致疑核运动神经元的明显细胞死亡，并诱导e-pF振荡器中节律发生的强烈改变。相比之下，preBotC振荡器似乎不受影响。这些缺陷导致上呼吸道功能受损、中枢呼吸节律产生异常以及对pH变化的反应改变。因此，一个单一的基因，Tshz 3，控制呼吸所需的电路的不同组件的发展。
Neonatal breathing in mammals involves multiple neuronal circuits, but its genetic basis remains unclear. Mice deficient for the zinc finger protein Teashirt 3 (TSHZ3) fail to breathe and die at birth. Tshz3 is expressed in multiple areas of the brainstem involved in respiration, including the pre-Botzinger complex (preBotC), the embryonic parafacial respiratory group (e-pF), and cranial motoneurons that control the upper airways. Tshz3 inactivation led to pronounced cell death of motoneurons in the nucleus ambiguus and induced strong alterations of rhythmogenesis in the e-pF oscillator. In contrast, the preBotC oscillator appeared to be unaffected. These deficits result in impaired upper airway function, abnormal central respiratory rhythm generation, and altered responses to pH changes. Thus, a single gene, Tshz3, controls the development of diverse components of the circuitry required for breathing.