Deschamps J, van den Akker E, Forlani S, De Graaff W, Oosterveen T, Roelen B, Roelfsema J
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
Int J Dev Biol. 1999;43(7):635-50.
Spatially and temporally restricted expression of the Hox genes along the main and appendicular axes is essential for correct patterning of vertebrate embryos. In this overview we discuss the latest data that shed light on the mechanisms underlying the generation of the expression domains of the Hox genes. The molecular genetic interactions governing initial transcription of the Hox genes in the posterior part of the primitive streak during mouse and chick gastrulation remain enigmatic. But the recent discovery by Kondo and Duboule (Cell, 97, 1999, 407-417) of a "cluster repressive regulation", will undoubtedly lead to a better understanding of the molecular genetic mechanism underlying colinear and sequential initiation of Hox gene transcription. Recently progress has been booked in characterizing the basal processes driving progression of the Hox expression domains during their establishment. Hox expression is still labile while being established. The transcriptional state of Hox genes in anterior tissues can be reprogrammed under the influence of more posterior locations. Posteriorizing activity may involve RA and FGF signaling. It is only when these interactions and, in some cases at least, regulatory interactions with Hox and cdx gene products occur appropriately, that the Hox expression domains would be correctly established. After the Hox expression domains have been established, regulatory processes involving the products of Polycomb and trithorax- Group genes start operating, perpetuating the transcriptional state of the Hox genes within and outside the expression domains. Whether control at the level of chromatin structure, believed to operate during the late maintenance phase of Hox gene expression, is also involved in regulating concerted initial expression of these genes, is a possibility that has been suggested.
Hox基因沿体轴和附肢轴在空间和时间上的受限表达对于脊椎动物胚胎的正确模式形成至关重要。在本综述中,我们讨论了最新数据,这些数据揭示了Hox基因表达域产生的潜在机制。在小鼠和鸡原肠胚形成期间,控制原条后部Hox基因初始转录的分子遗传相互作用仍然是个谜。但是近藤和杜布勒(《细胞》,第97卷,1999年,407 - 417页)最近发现的“簇抑制调控”,无疑将有助于更好地理解Hox基因转录共线性和顺序起始的分子遗传机制。最近在确定Hox表达域建立过程中驱动其进展的基础过程方面取得了进展。Hox表达在建立过程中仍然不稳定。前部组织中Hox基因的转录状态可以在更后部位置的影响下重新编程。后部化活性可能涉及视黄酸(RA)和成纤维细胞生长因子(FGF)信号传导。只有当这些相互作用以及至少在某些情况下与Hox和cdx基因产物的调控相互作用适当地发生时,Hox表达域才能正确建立。在Hox表达域建立之后,涉及多梳蛋白和三胸节基因产物的调控过程开始起作用,使Hox基因在表达域内外的转录状态得以维持。有人提出一种可能性,即被认为在Hox基因表达后期维持阶段起作用的染色质结构水平的控制,是否也参与调节这些基因的协同初始表达。