Danesh Shahab M, Villasenor Alethia, Chong Diana, Soukup Carrie, Cleaver Ondine
Department of Molecular Biology, NA8.300, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9148, USA.
Gene Expr Patterns. 2009 Jun;9(5):255-65. doi: 10.1016/j.gep.2009.04.002. Epub 2009 Apr 22.
Cell-cell communication is critical for regulating embryonic organ growth and differentiation. The Bone Morphogenetic Protein (BMP) family of transforming growth factor beta (TGFbeta) molecules represents one class of such cell-cell signaling molecules that regulate the morphogenesis of several organs. Due to high redundancy between the myriad BMP ligands and receptors in certain tissues, it has been challenging to address the role of BMP signaling using targeting of single Bmp genes in mouse models. Here, we present a detailed study of the developmental expression profiles of three BMP ligands (Bmp2, Bmp4, Bmp7) and three BMP receptors (Bmpr1a, Bmpr1b, and BmprII), as well as their molecular antagonist (noggin), in the early embryo during the initial steps of murine organogenesis. In particular, we focus on the expression of Bmp family members in the first organs and tissues that take shape during embryogenesis, such as the heart, vascular system, lungs, liver, stomach, nervous system, somites and limbs. Using in situ hybridization, we identify domains where ligand(s) and receptor(s) are either singly or co-expressed in specific tissues. In addition, we identify a previously unnoticed asymmetric expression of Bmp4 in the gut mesogastrium, which initiates just prior to gut turning and the establishment of organ asymmetry in the gastrointestinal tract. Our studies will aid in the future design and/or interpretation of targeted deletion of individual Bmp or Bmpr genes, since this study identifies organs and tissues where redundant BMP signaling pathways are likely to occur.
细胞间通讯对于调节胚胎器官的生长和分化至关重要。转化生长因子β(TGFβ)分子家族中的骨形态发生蛋白(BMP)代表了一类调节多个器官形态发生的细胞间信号分子。由于某些组织中众多BMP配体和受体之间存在高度冗余,在小鼠模型中通过靶向单个Bmp基因来研究BMP信号的作用一直具有挑战性。在此,我们详细研究了三种BMP配体(Bmp2、Bmp4、Bmp7)、三种BMP受体(Bmpr1a、Bmpr1b和BmprII)及其分子拮抗剂(noggin)在小鼠器官发生初始阶段早期胚胎中的发育表达谱。特别是,我们关注Bmp家族成员在胚胎发育过程中最早形成的器官和组织中的表达,如心脏、血管系统、肺、肝脏、胃、神经系统、体节和四肢。通过原位杂交,我们确定了配体和受体在特定组织中单独或共同表达的区域。此外,我们发现了Bmp4在胃系膜中的一种先前未被注意到的不对称表达,这种表达在肠道扭转和胃肠道器官不对称建立之前就开始了。我们的研究将有助于未来对单个Bmp或Bmpr基因靶向缺失的设计和/或解释,因为这项研究确定了可能存在冗余BMP信号通路的器官和组织。