Reversade Bruno, De Robertis E M
Howard Hughes Medical Institute and Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Cell. 2005 Dec 16;123(6):1147-60. doi: 10.1016/j.cell.2005.08.047.
Embryos have the ability to self-regulate and regenerate normal structures after being sectioned in half. How is such a morphogenetic field established? We discovered that quadruple knockdown of ADMP and BMP2/4/7 in Xenopus embryos eliminates self-regulation, causing ubiquitous neural induction throughout the ectoderm. ADMP transcription in the Spemann organizer is activated at low BMP levels. When ventral BMP2/4/7 signals are depleted, Admp expression increases, allowing for self-regulation. ADMP has BMP-like activity and signals via the ALK-2 receptor. It is unable to signal dorsally because of inhibition by Chordin. The ventral BMP antagonists Sizzled and Bambi further refine the pattern. By transplanting dorsal or ventral wild-type grafts into ADMP/BMP2/4/7-depleted hosts, we demonstrate that both poles serve as signaling centers that can induce histotypic differentiation over considerable distances. We conclude that dorsal and ventral BMP signals and their extracellular antagonists expressed under opposing transcriptional regulation provide a molecular mechanism for embryonic self-regulation.
胚胎在被切成两半后具有自我调节和再生正常结构的能力。这样一个形态发生场是如何建立的呢?我们发现,非洲爪蟾胚胎中ADMP和BMP2/4/7的四重敲低消除了自我调节能力,导致整个外胚层普遍发生神经诱导。斯佩曼组织者中ADMP的转录在低BMP水平时被激活。当腹侧BMP2/4/7信号缺失时,Admp表达增加,从而实现自我调节。ADMP具有类似BMP的活性,并通过ALK-2受体发出信号。由于受到脊索蛋白的抑制,它无法向背侧发出信号。腹侧BMP拮抗剂Sizzled和Bambi进一步细化了这种模式。通过将背侧或腹侧野生型移植物移植到ADMP/BMP2/4/7缺失的宿主中,我们证明两极都作为信号中心,能够在相当远的距离诱导组织型分化。我们得出结论,背侧和腹侧BMP信号及其在相反转录调控下表达的细胞外拮抗剂为胚胎自我调节提供了一种分子机制。