Mash1 regulates the development of C cells in mouse thyroid glands
Mash1 regulates the development of C cells in mouse thyroid glands
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DOI：
10.1002/dvdy.21018
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发表时间：
2007-01-01
影响因子：
2.5
通讯作者：
Guillemot, Francois
中科院分区：
文献类型：
--
作者：
Kameda, Yoko;Nishimaki, Toshiyuki;Guillemot, Francois
在哺乳动物中，源自第四咽囊的后鳃体产生甲状腺C细胞。新生小鼠的C细胞对降钙素、降钙素基因相关肽（CGRP）、蛋白基因产物（PGP）9.5和NeuroD具有免疫反应性，并且在胎儿发育期间短暂地表现出神经元标记TuJ 1和生长抑素。碱性螺旋-环-螺旋（bHLH）转录因子Mash 1在自主神经元的分化中起作用。我们发现，在野生型小鼠胚胎中，Mash 1在胚胎第12.5天（E）的后鳃体中表达，此时身体靠近大弓动脉。在E13.5，它也在与甲状腺叶融合的后鳃体中表达。Mash 1的靶向破坏导致小鼠甲状腺中缺乏C细胞，因为在胎儿发育期间或出生时未检测到显示C细胞标记物和表达NeuroD的细胞。无效突变甲状腺中C细胞形成的失败也通过电子显微镜证实。虽然Mash 1无效突变体的后鳃体的形成和迁移不受影响，但在E 12.5-E 13.5，位于动脉附近的后鳃体和甲状腺叶的器官都表现出凋亡细胞数量的显着增加。因此，在突变小鼠中，后鳃体未能完成其分化程序，最终死亡。这些结果表明，Mash 1通过抑制细胞凋亡来增强C细胞祖细胞的存活。
In mammals, the ultimobranchial body derived from the fourth pharyngeal pouch gives rise to thyroid C cells. The C cells of newborn mice are immunoreactive for calcitonin, calcitonin gene-related peptide (CGRP), protein gene product (PGP) 9.5 and NeuroD, and transiently exhibit the neuronal markers TuJ1 and somatostatin during fetal development. The basic helix-loop-helix (bHLH) transcription factor Mash1 plays a role in the differentiation of autonomic neurons. We show that in wild-type mouse embryos, Mash1 is expressed in the ultimobranchial body at embryonic day (E) 12.5, when the body is located close to the great arch arteries. It is also expressed in the ultimobanchial body fused with the thyroid lobe at E 13.5. Targeted disruption of Mash1 resulted in the absence of C cells in the mouse thyroid glands, since cells displaying the C-cell markers and expressing NeuroD were not detected during fetal development or at birth. The failure of C-cell formation in the null mutant thyroids was also confirmed by electron microscopy. While the formation and migration of the ultimobranchial body were not affected in the Mash1 null mutants, at E 12.5-E 13.5 both the ultimobranchial body located close to the arteries and the organ populating the thyroid lobe exhibited a marked increase in apoptotic cell numbers. Thus, in the mutant mice, the ultimobranchial body fails to complete its differentiation program and finally dies. These results indicate that Mash1 enhances survival of the C-cell progenitors by inhibiting apoptosis.