Furuta Y, Hogan B L
Howard Hughes Medical Institute and Department of Cell Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2175 USA.
Genes Dev. 1998 Dec 1;12(23):3764-75. doi: 10.1101/gad.12.23.3764.
Vertebrate lens development is a classical model system for studying embryonic tissue interactions. Little is known, however, about the molecules mediating such inductive events. Here, we show that Bmp4, which is expressed strongly in the optic vesicle and weakly in the surrounding mesenchyme and surface ectoderm, has crucial roles during lens induction. In Bmp4(tm1) homozygous null mutant embryos, lens induction is absent, but the process can be rescued by exogenous BMP4 protein applied into the optic vesicle in explant cultures. This is associated with rescue of ectodermal expression of Sox2, an early lens placode marker. Substituting the optic vesicle in explant cultures with BMP4-carrying beads, however, does not lead to lens induction, indicating that other factors produced by the optic vesicle are involved. BMP4 appears to regulate expression of a putative downstream gene, Msx2, in the optic vesicle. No change in Pax6 expression is seen in Bmp4(tm1) mutant eyes, and Bmp4 expression appears unaffected in the eyes of homozygous Pax6(Sey-1Neu), suggesting that PAX6 and BMP4 function independently. Based on these results we propose that BMP4 is required for the optic vesicle to manifest its lens-inducing activity, by regulating downstream genes and/or serving as one component of multiple inductive signals.
脊椎动物晶状体发育是研究胚胎组织相互作用的经典模型系统。然而，对于介导此类诱导事件的分子却知之甚少。在此，我们表明，在视泡中强烈表达而在周围间充质和表面外胚层中弱表达的Bmp4在晶状体诱导过程中起关键作用。在Bmp4(tm1)纯合无效突变胚胎中，晶状体诱导缺失，但通过在外植体培养中将外源性BMP4蛋白应用于视泡，该过程可以得到挽救。这与早期晶状体板标记物Sox2的外胚层表达的挽救相关。然而，用携带BMP4的珠子替换外植体培养中的视泡并不会导致晶状体诱导，这表明视泡产生的其他因子也参与其中。BMP4似乎调节视泡中一个假定的下游基因Msx2的表达。在Bmp4(tm1)突变眼中未观察到Pax6表达的变化，并且在纯合Pax6(Sey-1Neu)眼中Bmp4表达似乎未受影响，这表明PAX6和BMP4独立发挥作用。基于这些结果，我们提出BMP4是视泡通过调节下游基因和/或作为多个诱导信号的一个组成部分来表现其晶状体诱导活性所必需的。
