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Tbx3与Bmp4相互作用对腭发育过程中细胞增殖的调节作用。

Modulation of cell proliferation during palatogenesis by the interplay between Tbx3 and Bmp4.

作者信息

Lee Jong-Min, Kim Jae-Young, Cho Kyoung-Won, Lee Min-Jung, Cho Sung-Won, Zhang Yanding, Byun Seong-Kyu, Yi Choong-Kook, Jung Han-Sung

机构信息

Division in Anatomy and Developmental Biology, Department of Oral Biology, College of Dentistry, Yonsei University, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul, South Korea.

出版信息

Cell Tissue Res. 2007 Feb;327(2):285-92. doi: 10.1007/s00441-006-0271-8. Epub 2006 Oct 7.

DOI:10.1007/s00441-006-0271-8
PMID:17028893
Abstract

During secondary palate development, two shelves are elevated to a horizontal position above the tongue through a process involving many cellular mechanisms, including proliferation. In particular, the expression patterns of Tbx3 and Bmp4, which are colocalized at embryonic day 13.5 (E13.5) and have unique expression patterns in specific regions at E14.5, have been investigated in early mouse palatogenesis. Tbx3 expression is reported to be associated with Bmp4 signaling during the process of organogenesis in other areas, such as limb development. However, the function of Tbx3 and the relationship between Tbx3 and Bmp4 in palate development have not been determined. We have examined the gene expression pattern and cell proliferation in order to understand the mutual interactions and function of Tbx3 and Bmp4. An electroporation method was used to investigate the altered pattern of these genes after their over-expression in organ cultures. NOGGIN protein-soaked beads were also implanted into the cultured palate to determine the function of Bmp4 in palatogenesis. After electroporation and NOGGIN bead implantation, the number of PCNA-positive cells was counted. The results showed that Tbx3 and Bmp4 strongly up- and down-regulated each other in order to control the proliferation of the palatal shelf. Thus, Tbx3 expression is induced by Bmp4 in the mesenchyme of the anterior palatal shelves, whereas mesenchymal expression of Tbx3 down-regulates Bmp4 expression in the mesenchyme of the palate. The harmonization between Tbx3 and Bmp4 therefore controls cell proliferation to regulate secondary palate development.

摘要

在次生腭发育过程中,两个腭突通过一个涉及多种细胞机制(包括增殖)的过程升高至舌头上方的水平位置。特别是,在小鼠早期腭发育过程中,对Tbx3和Bmp4的表达模式进行了研究,它们在胚胎第13.5天(E13.5)共定位,在E14.5的特定区域具有独特的表达模式。据报道,在其他区域(如肢体发育)的器官发生过程中,Tbx3表达与Bmp4信号传导相关。然而,Tbx3在腭发育中的功能以及Tbx3与Bmp4之间的关系尚未确定。为了了解Tbx3和Bmp4的相互作用和功能,我们检测了基因表达模式和细胞增殖情况。采用电穿孔法研究这些基因在器官培养物中过表达后的变化模式。还将浸泡有NOGGIN蛋白的珠子植入培养的腭中,以确定Bmp4在腭发育中的功能。在电穿孔和NOGGIN珠子植入后,对PCNA阳性细胞的数量进行计数。结果表明,Tbx3和Bmp4为了控制腭突的增殖而相互强烈上调和下调。因此,在前腭突间充质中,Bmp4诱导Tbx3表达,而Tbx3在腭间充质中的表达下调Bmp4表达。因此,Tbx3和Bmp4之间的协调控制细胞增殖以调节次生腭发育。

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引用本文的文献

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Dev Biol. 2018 Dec 1;444 Suppl 1(Suppl 1):S337-S351. doi: 10.1016/j.ydbio.2018.09.017. Epub 2018 Oct 5.
2
Development of Normal and Cleft Palate: A Central Role for Connective Tissue Growth Factor (CTGF)/CCN2.正常腭与腭裂的发育:结缔组织生长因子(CTGF)/CCN2的核心作用
J Dev Biol. 2018 Jul 19;6(3):18. doi: 10.3390/jdb6030018.
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Tbx3 represses bmp4 expression and, with Pax6, is required and sufficient for retina formation.
Tbx3抑制bmp4的表达,并且与Pax6一起,对视网膜形成是必需的且足够的。
Development. 2016 Oct 1;143(19):3560-3572. doi: 10.1242/dev.130955. Epub 2016 Aug 30.
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MicroRNA-17-92, a direct Ap-2α transcriptional target, modulates T-box factor activity in orofacial clefting.miR-17-92,一个直接的 Ap-2α 转录靶标,调节口腔面裂中 T 盒因子的活性。
PLoS Genet. 2013;9(9):e1003785. doi: 10.1371/journal.pgen.1003785. Epub 2013 Sep 19.
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