Belo J A, Bachiller D, Agius E, Kemp C, Borges A C, Marques S, Piccolo S, De Robertis E M
Genesis. 2000 Apr;26(4):265-70.
Mouse cerberus-like (cer-l) is a member of the Cerberus/Dan family of secreted factors. As other members of this family of proteins, Cer-l functions in the extracellular space, inhibiting signaling molecules. Here we show that the neural-inducing and mesoderm-inhibiting activities of Cer-l result from specific binding to BMP and Nodal molecules, respectively. These properties resemble the ones from the related factor Xenopus Cerberus. However, Xenopus Cerberus in addition to BMP4 and Nodal also binds to and inhibits Wnt proteins. We show that Cer-l does not directly inhibit Wnt signals. A null allele of the mouse Cer-l gene was generated by targeted inactivation in ES cells. Homozygous embryos show no anterior patterning defects, are born alive, and are fertile. Since mouse Cer-l and Xenopus Cerberus differ in biochemical activities, we propose the existence of additional members of this family of inhibitors, which may compensate for the loss of cer-l.
小鼠类大脑神经因子（Cer-l）是分泌因子Cerberus/Dan家族的成员之一。与该蛋白家族的其他成员一样，Cer-l在细胞外空间发挥作用，抑制信号分子。我们在此表明，Cer-l的神经诱导和中胚层抑制活性分别源于其与骨形态发生蛋白（BMP）和Nodal分子的特异性结合。这些特性与相关因子非洲爪蟾Cerberus的特性相似。然而，非洲爪蟾Cerberus除了与BMP4和Nodal结合外，还与Wnt蛋白结合并抑制其活性。我们发现Cer-l并不直接抑制Wnt信号。通过在胚胎干细胞中进行靶向失活，产生了小鼠Cer-l基因的无效等位基因。纯合子胚胎未表现出前轴模式缺陷，能够存活且具有生育能力。由于小鼠Cer-l和非洲爪蟾Cerberus在生化活性上存在差异，我们推测该抑制因子家族可能存在其他成员，它们或许能够补偿Cer-l缺失带来的影响。
