Teashirt 1 (Tshz1) is essential for the development, survival and function of hypoglossal and phrenic motor neurons in mouse
Teashirt 1 (Tshz1) is essential for the development, survival and function of hypoglossal and phrenic motor neurons in mouse
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DOI：
10.1242/dev.174045
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发表时间：
2019-09-01
期刊：
影响因子：
4.6
通讯作者：
Birchmeier, Carmen
中科院分区：
文献类型：
--
作者：
Chaimowicz, Charlotte;Ruffault, Pierre-Louis;Birchmeier, Carmen
进食和呼吸是基本的运动功能，依赖于支配舌头和隔膜的舌下和膈运动神经元的活动。分别。人们对控制这些神经元亚型发育的遗传程序知之甚少。转录因子Tshz1在发育中的舌下和膈运动神经元中持续强烈表达。我们使用运动神经元祖区Tshz1的条件突变（Tshz1(MN δ)）来证明Tshz1对舌下和膈下运动神经元的存活和功能至关重要。在Tshz1（MN Delta）突变小鼠中，舌下和膈下运动神经元的出生数量是正确的，但许多神经元在胚胎期13.5天至14.5天之间死亡。此外，膈和舌下运动神经元的神经支配和电生理特性发生改变。严重的喂养和呼吸问题伴随着这种发育缺陷。虽然通过消除促凋亡因子Bax可以挽救运动神经元的存活，但Bax的神经支配、摄食和呼吸缺陷持续存在（-/-）；Tshz1（MN δ）突变体。我们认为Tshz1是膈和舌下运动神经元发育和生理功能的重要转录因子。
Feeding and breathing are essential motor functions and rely on the activity of hypoglossal and phrenic motor neurons that innervate the tongue and diaphragm. respectively. Little is known about the genetic programs that control the development of these neuronal subtypes. The transcription factor Tshz1 is strongly and persistently expressed in developing hypoglossal and phrenic motor neurons. We used conditional mutation of Tshz1 in the progenitor zone of motor neurons (Tshz1(MN Delta))to show that Tshz1 is essential for survival and function of hypoglossal and phrenic motor neurons. Hypoglossal and phrenic motor neurons are born in correct numbers, but many die between embryonic day 13.5 and 14.5 in Tshz1(MN Delta) mutant mice. In addition, innervation and electrophysiological properties of phrenic and hypoglossal motor neurons are altered. Severe feeding and breathing problems accompany this developmental deficit. Although motor neuron survival can be rescued by elimination of the proapoptotic factor Bax, innervation, feeding and breathing defects persist in Bax(-/-); Tshz1(MN Delta) mutants. We conclude that Tshz1 is an essential transcription factor for the development and physiological function of phrenic and hypoglossal motor neurons.