BMP in somite, cartilage and bone development

本研究的主要目的是研究骨骼发育对骨形态发生蛋白（BMP）信号的需求。bmp是转化生长因子- β细胞因子家族的成员，在脊椎动物发育过程中发挥着各种不同的作用。bmp最初是因其诱导骨骼的能力而被发现的，但它们也调节着许多其他过程。BMP Ia型受体主要转导BMP2和BMP4信号。该受体在胚胎发生和成人组织中广泛表达，表明该受体可以介导多种组织中的BMP信号。编码BMP型IA受体的Bmp4基因发生靶向突变的纯合子小鼠在发育早期死亡，未形成中胚层。此外，从Bmpr突变胚胎中产生的畸胎瘤表明，Bmpr -/-细胞具有分化为某些中胚层来源组织的能力，包括骨骼肌和软骨。Bmpr突变体的早期致命性阻碍了它们在胚胎发生后期或成体组织中通过BMP型IA受体进行信号传导的研究。我们在小鼠胚胎干（ES）细胞中通过基因靶向产生了Bmpr的条件loxp - flanxed （floxed）等位基因。结合在特定组织中表达cre重组酶的转基因小鼠，我们打算研究BMP信号在体体、软骨和骨发育中的作用。这种条件遗传系统应该导致新的见解关于骨骼系统发育中的BMP信号。

The primary goal of this proposal is to investigate the requirement of bone morphogenetic protein (BMP) signals in skeletal development. BMPs are members of the transforming growth factor-beta family of cytokines that play a variety of different roles during vertebrate development. BMPs were first identified for their bone-inducing abilities but they also regulate many other processes. The BMP type Ia receptor primary transduces BMP2 and BMP4 signals. This receptor is widely expressed during embryogenesis and in adult tissues, suggesting that this receptor can mediate BMP signals in many tissues. Mice that are homozygous for a targeted mutation in the Bmp4 gene that encodes the BMP type IA receptor die early in development without forming mesoderm. In addition, teratomas generated from Bmpr mutant embryos suggested that Bmpr -/- cells are comprised their abilities to differentiate into certain mesodermally-derived tissues, including skeletal muscle and cartilage. The early lethality of the Bmpr mutants precludes their usefulness in investigating the role of signaling through the BMP type IA receptor at later stages of embryogenesis or in adult tissues. We have generated a conditional loxP-flanked (floxed) allele of Bmpr in mice by gene targeting in mouse embryonic stem (ES) cells. In combination with transgenic mice that express cre recombinase in specific tissues, we propose to examine the role of BMP signals in somite, cartilage and bone development. This conditional genetic system should lead to new insights regarding BMP signals in the development of the skeletal system.