Characterization of the receptors for secretory signaling proteins involved in inductive interaction during embryogenesis

我们已经确定了BMP、Sonic Hedgehog(Shh)和Wnt家族的受体在脊椎动物发育过程中参与器官发生的特征。我们从鸡胚胎中鉴定出三种BMP受体，分别称为BRK-1(ALK-3)、BRK-2(ALK-6)和BRK-3(BMPRII)。BRK-2和BRK-3构成BMP-4同源二聚体的高亲和力受体系统，在肢芽软骨前间充质中表达，而BRK-1在肢芽中低表达。当缺陷型BRK-2和BRK-3受体与逆转录病毒载体在肢芽中共表达时，BRK-2和BRK-3的激活域缺陷形式抑制了肢体间充质细胞向软骨细胞的分化，最终导致指骨缺陷；Shh可诱导BMP-2基因和BRK-2受体基因的表达。在应用…后不久，Shh还上调了编码Shh受体的补丁基因在肢体间充质中的表达Shh诱导的HoxD基因和其他标记基因的表达模式的时间进程表明，BMP信号参与了早期肢芽位置的确定。Wnt家族的几个成员以特殊的模式在肢芽中表达，Wnt-5a在第19-26期显示了远端的表达区域。过表达Wnt-5a基因导致了斑足类动物基因的截断，但不影响HoxD和HoxA的表达。我们分离了几个编码Wnt家族跨膜受体的Frizzleed(FZ)cDNA，它们的表达模式表明Wnt信号参与了肢体芽中指定区域身份的过程。FZ-4在肢芽的顶端外胚脊和远端间充质中表达，而新的FZ-10基因在背侧间充质的后-远端区域表达。FZ-6在体节中表达，FZ-3和FZ-10在神经管中表达，提示它们在Wnt-3a和Wnt-7a信号转导中发挥作用。较少

We have characterized the receptors for BMP,Sonic hedgehog (Shh), and Wnt family involved in organogenesis during vertebrate development. We identified three BMP receptors, called BRK-1 (ALK-3), BRK-2 (ALK-6), and BRK-3 (BMPRII), from the chick embryo. BRK-2 abd BRK-3 constitute high affinity receptor system for BMP-4 homodimer, and are expressed in the precartilagenous mesenchyme of the limb bud, whereas BRK-1 is poorly expressed in the limb bud. Kinase domain-deficient forms of BRK-2 and BRK-3 inhibited chondrogenic differentiation of limb mesenchymal cells, eventually leading to defects in the digital bones, when the defective receptors were co-expressed in the limb bud with retrovirus vector.Shh could induce expression of the BMP-2 gene and also the BRK-2 receptor gene, when Shh was applied to the anterior limb bud by using either retrovirus or recombinant protein. The Patched gene encoding the Shh receptor was also upregulated in the limb mesenchyme by Shh shortly after applicatio … More n. The time course of the Shh-induced expression pattern of the HoxD genes and other marker genes suggests BMP signaling is implicated in determination of positional identity in the limb bud at early stages.Several Wnt family members are expressed in the limb bud with speciffic pattern, and Wnt-5a reveals distal expression domain at stages 19-26. Over-expressing the Wnt-5a gene resulted in the truncation of zeugopod, but did not affect HoxD and HoxA expression. We isolated several Frizzled (Fz) cDNAs encoding the transmembrane receptors for Wnt family, and their expression patterns indicate involvement of Wnt signaling in specifying regional identity in the limb bud. The Fz-4 is expressed in the apical ectodermal ridge and distal mesenchyme of the limb bud, whereas the novel Fz-10 gene is expressed in the posterior-distal region of the dorsal mesenchyme. Fz-6 is expressed in the somite, and Fz-3 and Fz-10 are expressed in the neural tube, suggesting their roles in Wnt-3a and Wnt-7a signaling. Less