Neural crest-specific deletion of Ldb1 leads to cleft secondary palate with impaired palatal shelf elevation.
Neural crest-specific deletion of Ldb1 leads to cleft secondary palate with impaired palatal shelf elevation.
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DOI：
10.1186/1471-213x-14-3
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发表时间：
2014-01-17
影响因子：
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通讯作者：
Jeong J
中科院分区：
文献类型：
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作者：
Almaidhan A;Cesario J;Landin Malt A;Zhao Y;Sharma N;Choi V;Jeong J
LIM结构域结合蛋白1（LDB 1）是一种转录辅因子，与多种转录因子及其它含有LIM结构域的蛋白相互作用。小鼠Ldb 1完全失活导致早期胚胎死亡，原肠胚形成过程中出现严重的图案缺陷。使用条件性敲除等位基因的组织特异性缺失揭示了Ldb 1在中枢神经系统、造血系统和四肢发育中的额外作用。本研究的目的是确定Ldb 1功能在小鼠胚胎颅面发育过程中的重要性。我们使用Wnt 1-Cre产生了组织特异性Ldb 1突变体，该突变体导致神经嵴中的floxed等位基因缺失;神经嵴衍生的细胞有助于发育中的面部的大部分间充质。所有检测的Wnt 1-Cre; Ldb 1 fl/-突变体均患有继发性腭裂。因此，我们进行了一系列实验来研究Ldb 1如何调节味觉发育。首先，我们研究了Ldb 1在正常发育过程中的表达，发现Ldb 1在腭发育的早期阶段广泛表达于腭间充质中。其次，我们比较了形态学的发育腭在控制和Ldb 1突变体胚胎使用部分。我们发现，突变腭架有异常钝的外观，并未能提高以上的舌头在后域。体外头部培养实验表明，海拔缺陷是由于干扰的舌头。最后，在Ldb 1突变腭架，细胞增殖异常的前部，和Wnt 5a，Pax 9和Osr 2的表达，调节腭架海拔，也被改变。Ldb 1在神经嵴来源的腭间充质中的功能对于次级腭的正常形态发生是必不可少的。
LIM domain binding protein 1 (LDB1) is a transcriptional co-factor, which interacts with multiple transcription factors and other proteins containing LIM domains. Complete inactivation of Ldb1 in mice resulted in early embryonic lethality with severe patterning defects during gastrulation. Tissue-specific deletions using a conditional knockout allele revealed additional roles of Ldb1 in the development of the central nervous system, hematopoietic system, and limbs. The goal of the current study was to determine the importance of Ldb1 function during craniofacial development in mouse embryos. We generated tissue-specific Ldb1 mutants using Wnt1-Cre, which causes deletion of a floxed allele in the neural crest; neural crest-derived cells contribute to most of the mesenchyme of the developing face. All examined Wnt1-Cre;Ldb1 fl/- mutants suffered from cleft secondary palate. Therefore, we performed a series of experiments to investigate how Ldb1 regulated palate development. First, we examined the expression of Ldb1 during normal development, and found that Ldb1 was expressed broadly in the palatal mesenchyme during early stages of palate development. Second, we compared the morphology of the developing palate in control and Ldb1 mutant embryos using sections. We found that the mutant palatal shelves had abnormally blunt appearance, and failed to elevate above the tongue at the posterior domain. An in vitro head culture experiment indicated that the elevation defect was not due to interference by the tongue. Finally, in the Ldb1 mutant palatal shelves, cell proliferation was abnormal in the anterior, and the expression of Wnt5a, Pax9 and Osr2, which regulate palatal shelf elevation, was also altered. The function of Ldb1 in the neural crest-derived palatal mesenchyme is essential for normal morphogenesis of the secondary palate.