Requirement for integrin-linked kinase in neural crest migration and differentiation and outflow tract morphogenesis.
Requirement for integrin-linked kinase in neural crest migration and differentiation and outflow tract morphogenesis.
复制标题
神经嵴迁移和分化以及流出道形态发生对整合素连接激酶的要求
DOI：
10.1186/1741-7007-11-107
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发表时间：
2013-10-16
期刊：
影响因子：
5.4
通讯作者：
Liang X
中科院分区：
文献类型：
--
作者：
Dai X;Jiang W;Zhang Q;Xu L;Geng P;Zhuang S;Petrich BG;Jiang C;Peng L;Bhattacharya S;Evans SM;Sun Y;Chen J;Liang X
背景：神经嵴缺损导致先天性心脏病伴流出道畸形。整合素连接激酶（Integrin-linked-kinase， ILK）在多种细胞过程和胚胎发生中发挥重要作用。ILK在神经嵴中表达，但其在神经嵴和流出道形态发生中的作用尚不清楚。结果利用Wnt1-Cre基因在神经嵴特异地消融了ILK。ILK消融导致咽弓和流出道神经嵴细胞异常迁移和过度聚集，神经细胞粘附分子（NCAM）和细胞外基质成分的表达显著降低。ILK突变胚胎表现为总动脉干增大和室间隔缺损。在ILK突变体流出道中观察到平滑肌分化减少，但骨化和神经发生/神经支配增加，部分原因可能是转化生长因子β2 （tgf - β2）减少，而骨形态发生蛋白（BMP）信号传导增加。与这些观察结果一致，荧光激活细胞分选（FACS）分选神经嵴细胞的微阵列分析显示，与肌肉分化相关的基因表达减少，但神经发生和成骨基因表达增加。结论研究结果表明，ILK通过介导细胞基质与多种信号通路之间的复杂串扰，在神经嵴和神经流出道发育中发挥重要作用。这些通路的改变可能共同导致在ILK突变体中观察到的独特的神经嵴和流出道表型。
BackgroundNeural crest defects lead to congenital heart disease involving outflow tract malformation. Integrin-linked-kinase (ILK) plays important roles in multiple cellular processes and embryogenesis. ILK is expressed in the neural crest, but its role in neural crest and outflow tract morphogenesis remains unknown.ResultsWe ablated ILK specifically in the neural crest using the Wnt1-Cre transgene. ILK ablation resulted in abnormal migration and overpopulation of neural crest cells in the pharyngeal arches and outflow tract and a significant reduction in the expression of neural cell adhesion molecule (NCAM) and extracellular matrix components. ILK mutant embryos exhibited an enlarged common arterial trunk and ventricular septal defect. Reduced smooth muscle differentiation, but increased ossification and neurogenesis/innervation were observed in ILK mutant outflow tract that may partly be due to reduced transforming growth factor β2 (TGFβ2) but increased bone morphogenetic protein (BMP) signaling. Consistent with these observations, microarray analysis of fluorescence-activated cell sorting (FACS)-sorted neural crest cells revealed reduced expression of genes associated with muscle differentiation, but increased expression of genes of neurogenesis and osteogenesis.ConclusionsOur results demonstrate that ILK plays essential roles in neural crest and outflow tract development by mediating complex crosstalk between cell matrix and multiple signaling pathways. Changes in these pathways may collectively result in the unique neural crest and outflow tract phenotypes observed in ILK mutants.
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影响因子：
64.5
作者：
Merscher, S;Funke, B;Kucherlapati, R
通讯作者：
Kucherlapati, R
影响因子：
13.5
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2.7
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10.5
作者：
FASSLER, R;MEYER, M
通讯作者：
MEYER, M
影响因子：
25
作者：
Madisen L;Zwingman TA;Sunkin SM;Oh SW;Zariwala HA;Gu H;Ng LL;Palmiter RD;Hawrylycz MJ;Jones AR;Lein ES;Zeng H
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