The T-box transcription factor Tbx18 maintains the separation of anterior and posterior somite compartments

The T-box transcription factor Tbx18 maintains the separation of anterior and posterior somite compartments
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DOI:
10.1101/gad.300104
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发表时间:
2004-05-15
影响因子:
10.5
通讯作者:
Kispert, A
Kispert, A
中科院分区:
生物学1区
文献类型:
--
作者:
Bussen, M;Petry, M;Kispert, A

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体节沿着其前后轴(AP)的区室化对于脊椎动物中轴骨骼和周围神经系统的节段性组织至关重要。体节的前半部分和后半部分构成不同的椎骨成分。它们的特征还在于不同的增殖速率和关于神经嵴细胞迁移和脊神经通过的性质。AP-体节极性是由Mesp 2和Delta/Notch信号在前体前中胚层中产生的。在这里,我们表明,AP-体节极性的维护是由T-box转录因子Tbx 18介导的。Tbx 18缺陷的小鼠显示出具有横突和近端肋的椎弓根的扩张,这些元件来自后外侧硬骨节。AP-体节极性在Tbx 18突变体胚胎中建立,但不维持。在体节成熟过程中,后体节室的扩大很可能是因为后细胞侵入前半体节。在前外侧巩膜中,Tbx 18作为抗凋亡因子。异位表达实验表明,Tbx 18可以促进前在后体节室的费用。总之,Tbx 18似乎作用于Mesp 2和Delta/Notch信号传导的下游,以维持前体节隔室和后体节隔室的分离。
The compartmentalization of somites along their anterior-posterior (AP) axis is pivotal to the segmental organization of the vertebrate axial skeleton and the peripheral nervous system. Anterior and posterior somite halves contribute to different vertebral elements. They are also characterized by different proliferation rates and properties with respect to neural crest cell migration and spinal nerve passage. AP-somite polarity is generated in the anterior presomitic mesoderm by Mesp2 and Delta/Notch signaling. Here, we demonstrate that maintenance of AP-somite polarity is mediated by the T-box transcription factor Tbx18. Mice deficient for Tbx18 show expansion of pedicles with transverse processes and proximal ribs, elements derived from the posterior lateral sclerotome. AP-somite polarity is established in Tbx18 mutant embryos but is not maintained. During somite maturation, posterior somite compartments expand most likely because of posterior cells invading the anterior somite half. In the anterior lateral sclerotome, Tbx18 acts as an antiapoptotic factor. Ectopic expression experiments suggest that Tbx18 can promote anterior at the expense of posterior somite compartments. In summary, Tbx18 appears to act downstream of Mesp2 and Delta/Notch signaling to maintain the separation of anterior and posterior somite compartments.