Pathways controlling cell fate decisions in the early mouse embryo

Abstract

22 will be presented as scheduled, but will not be published due to lack of license agreement between authors and publisher. doi:10.1016/j.ydbio.2009.05.029 Program/Abstract # 23 Pathways controlling cell fate decisions in the early mouse embryo Elizabeth J. Robertson, Sebastian Arnold, Mathias Groszer, Elizabeth Bikoff Department of Pathology, Univ of Oxford, Oxford, UK Wellcome Trust Centre Human Genetics, Univ of Oxford, UK TGFβ pathways are instrumental in patterning the somatic lineages of the early mouse embryo, as well as for formation of the germ line. Previous experiments argue that graded Nodal activities control the very earliest cell fate decisions during axis patterning, and are essential for correct mesodermal patterning and specification of axial mesendoderm and definitive endoderm. During gastrulation high levels of nodal induce endoderm progenitors, whereas lower levels specify mesoderm. In addition Nodal directly acts to maintain undifferentiated trophoblast stem cells within the extraembryonic ectoderm and thereby maintain the expression of Bmp4 required for germ cell specification. Our recent studies show that the Tbox transcription factor Eomesodermin (Eomes), acting downstream of nodal signalling, plays multiple roles in the developing embryo. Eomes activities in the trophectoderm are required for maintaining trophoblast stem cells, while in the epiblast Eomes has two roles namely to promote nascent mesoderm to undergo EMT during gastrulation, and for specification of the definitive endoderm lineage. Interestingly Eomes is also transiently expressed in the subventricular zone of the developing cortex. Sox1.Cre mediated deletion causes microcephaly and severe behavioural defects. This can be attributed to a reduction in the expansion of the SVZ progenitor cells leading to a disturbance in the formation of upper cortical neurons. Thus Eomes has emerged as a key regulator of multiple processes in the mouse embryo. doi:10.1016/j.ydbio.2009.05.030 Program/Abstract # 24 Localized Xenopus Trim36 regulates cortical rotation and dorsal axis formation Douglas W. Houston, Tawny N. Cuykendall Department of Biology, The University of Iowa, Iowa City, IA, USA The activation of Wnt/beta-catenin signaling on the future dorsal side of the blastula is necessary and sufficient for axis formation in Xenopus and other vertebrates. Wnt signaling is initiated by dorsal enrichment of vegetally localized molecules following rotation of the egg cortex after fertilization. Both localized wnt11 mRNA and protein inhibitors of beta-catenin degradation, Dishevelled and GBP, have been implicated, but the mechanisms activating Wnt signaling in axis formation still remain elusive. Because vegetally localized RNAs are important for this process, we have conducted a microarray screen to identify novel mRNAs localized to the vegetal cortex. We present evidence that a localized mRNA encoding a Tripartite Motif Protein (Trim), Trim36, plays a critical role in Xenopus axis formation. Maternal antisense inhibition of Trim36 resulted in ventralized embryos, with reductions in dorsal beta-catenin accumulation and Wnt target gene expression. We further present experiments to identify the extent that Trim36 interacts with Wnt/beta-catenin signaling and cortical rotation mechanisms. doi:10.1016/j.ydbio.2009.05.031 Abstracts / Developmental Biology 331 (2009) 390–391 391