CAA: Role of Extracellular Matrix Proteins in Craniofacial Development in Mammals

在哺乳动物头面部发育过程中，研究人员正在研究两种细胞外基质蛋白--肌腱蛋白和凝血酶反应蛋白的表达模式。这些蛋白质被认为在肌腱发育、骨化过程、结缔组织模式的建立以及其他一些发育事件中都具有重要意义。两个模型系统--小鼠和小负鼠--将被用来检验这些假设。具体研究包括：利用PCR克隆技术构建针对Tenascin的有袋类cDNA探针；利用这些探针定位Tenascin在发育中的有袋新生儿颅骨组织中的时空表达；Monodelphis与小鼠表达模式的比较；为未来的一项研究收集先导数据，该研究涉及通过应用外源生长因子对体内基质基因表达的实验性操纵；以及小鼠胚胎中凝血酶反应蛋白表达的时间和空间图谱。这个项目意义重大，原因有很多。首先，它将允许对正常颅面发育所涉及的过程进行检查，并可能有助于阐明两个被认为在发育中具有普遍意义的分子的重要性。其次，它将利用一种新的哺乳动物发育模式--家养单胞菌，在这种模式下，大多数发育发生在出生后。此外，这些研究还将探索在有袋类和胎盘类哺乳动物发育中观察到的异时性的分子基础。最后，根据职业发展奖的目标，该项目将提供机会，将以前的研究扩展到全新的方向。

The pattern of expression of two extracellular matrix proteins, tenascin and thrombospondin, is being examined during craniofacial development in mammals. These proteins are thought to be significant in musculosketetal development, in the process of ossification, in the establishment of connective tissue patterning, as well as in a number of other developmental events. Two model systems -- mice and the mini-opossum, Monodelphis domestica -- will be used to test these hypotheses. Specific studies include: the use of PCR cloning techniques to contruct a marsupial cDNA probe to tenascin; the use of these probes to map the spatial and temporal expression of tenascin in cranial skeletal tissues in the developing marsupial neonate; the comparison of the pattern of expression in Monodelphis with that in mice; the collection of pilot data for a future study involving the experimental manipulation of matrix gene expression in vivo by application of exogenous growth factors; and the mapping of expression of thrombospondin in time and space in mic embryos. This project is significant for a number of reasons. First, it will allow an examination of the processes involved in normal craniofacial development and may help illuminate the significance of two molecules thought to be of general significance in development. Second, it will make use of a new model for mammalian development, Monodelphis domestica, in which most development occurs after birth. Additionally, these studies will allow exploration of the molecular basis of heterochronies observed in marsupial and placental mammal development. Finally, in line with the goals of the Career Advancement Award, this project will provide the opportunity to extend previous research into entirely new directions.