Divergent functions and distinct localization of the Notch ligands DLL1 and DLL3 in vivo.

Divergent functions and distinct localization of the Notch ligands DLL1 and DLL3 in vivo.
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DOI:
10.1083/jcb.200702009
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发表时间:
2007-07-30
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Gossler A
Gossler A
中科院分区:
其他
文献类型:
--
作者:
Geffers I;Serth K;Chapman G;Jaekel R;Schuster-Gossler K;Cordes R;Sparrow DB;Kremmer E;Dunwoodie SL;Klein T;Gossler A

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Notch配体DLL1和DLL3在小鼠胚胎的中胚层中共表达。尽管DLL1和DLL3基因共表达,但它们的突变会导致截然不同的缺陷。为了确定是否存在任何功能等价性,我们在小鼠身上用DLL3取代了DLL1。DLL3不补偿DLL1;DLL1激活果蝇翼盘上的Notch,但DLL3不补偿。我们没有观察到DLL1和DLL3之间有拮抗作用的证据,也没有证据表明DLL1和DLL3对小鼠或果蝇的Notch活性有抑制作用。体外分析表明,DLL1和DLL3不同结构域的差异分别导致了它们的生化不等价性。与位于分裂前中胚层细胞表面的内源性DLL1相反,我们发现内源性DLL3主要存在于高尔基体。我们的数据显示了DLL1和DLL3在体内的不同功能。提示DLL3不拮抗DLL1在卵裂期前中胚层中的作用,值得进一步分析DLL3在高尔基体网络中的潜在生理功能。
The Notch ligands Dll1 and Dll3 are coexpressed in the presomitic mesoderm of mouse embryos. Despite their coexpression, mutations in Dll1 and Dll3 cause strikingly different defects. To determine if there is any functional equivalence, we replaced Dll1 with Dll3 in mice. Dll3 does not compensate for Dll1; DLL1 activates Notch in Drosophila wing discs, but DLL3 does not. We do not observe evidence for antagonism between DLL1 and DLL3, or repression of Notch activity in mice or Drosophila. In vitro analyses show that differences in various domains of DLL1 and DLL3 individually contribute to their biochemical nonequivalence. In contrast to endogenous DLL1 located on the surface of presomitic mesoderm cells, we find endogenous DLL3 predominantly in the Golgi apparatus. Our data demonstrate distinct in vivo functions for DLL1 and DLL3. They suggest that DLL3 does not antagonize DLL1 in the presomitic mesoderm and warrant further analyses of potential physiological functions of DLL3 in the Golgi network.
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