Subject(s)
Bence Jones Protein , Multiple Myeloma , Gels , Humans , Immunoelectrophoresis , Immunologic Tests , ProteinuriaABSTRACT
During amphibian development, neural patterning occurs via a two-step process. Spemann's organizer secretes BMP antagonists that induce anterior neural tissue. A subsequent caudalizing step re-specifies anterior fated cells to posterior fates such as hindbrain and spinal cord. The neural patterning paradigm suggests that a canonical Wnt-signaling gradient acts along the anteroposterior axis to pattern the nervous system. Wnt activity is highest in the posterior, inducing spinal cord, at intermediate levels in the trunk, inducing hindbrain, and is lowest in anterior fated forebrain, while BMP-antagonist levels are constant along the axis. Our results in Xenopus laevis challenge this paradigm. We find that inhibition of canonical Wnt signaling or its downstream transcription factors eliminates hindbrain, but not spinal cord fates, an observation not compatible with a simple high-to-low Wnt gradient specifying all fates along the neural anteroposterior axis. Additionally, we find that BMP activity promotes posterior spinal cord cell fate formation in an FGF-dependent manner, while inhibiting hindbrain fates. These results suggest a need to re-evaluate the paradigms of neural anteroposterior pattern formation during vertebrate development.
Subject(s)
Body Patterning , Bone Morphogenetic Proteins/metabolism , Nervous System/embryology , Nervous System/metabolism , Neurogenesis , Signal Transduction , Wnt Proteins/metabolism , Animals , Bone Morphogenetic Proteins/genetics , Ectoderm/embryology , Ectoderm/metabolism , Fibroblast Growth Factors/metabolism , Gene Expression Regulation, Developmental , Mesoderm/embryology , Mesoderm/metabolism , Rhombencephalon/embryology , Rhombencephalon/metabolism , Spinal Cord/embryology , Spinal Cord/metabolism , Xenopus laevisABSTRACT
Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior-posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox-TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001.
Subject(s)
Body Patterning , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Evolution, Molecular , Homeodomain Proteins/metabolism , Transcription Factors/metabolism , Xenopus Proteins/metabolism , Xenopus/metabolism , Animals , Animals, Genetically Modified , Binding Sites , Drosophila Proteins/genetics , Drosophila melanogaster/embryology , Drosophila melanogaster/genetics , Gene Expression Regulation, Developmental , Homeodomain Proteins/genetics , Phylogeny , Promoter Regions, Genetic , Protein Binding , Sea Anemones/embryology , Sea Anemones/genetics , Sea Anemones/metabolism , Species Specificity , Transcription Factors/genetics , Xenopus/embryology , Xenopus/genetics , Xenopus Proteins/geneticsABSTRACT
Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea among infants and children in developing countries, as well as among travelers to these areas. The major virulence factors of ETEC are the colonization factor antigens (CFAs) and a heat-labile enterotoxin (LT) and/or a heat-stable enterotoxin (ST). Among Israeli recruits serving under military field conditions, 107 of all examined isolates expressed LT or ST, and CFAs could be characterized in 68% of the isolates, in which CFAs of the CFA/II group and CS6 were the most prevalent. Additionally, 31% of the 107 ETEC isolates showed resistance to three or more of the antimicrobial agents examined, and the percentage of resistant isolates expressing LT was significantly higher than those expressing ST or LT+ST. These results may be important for development of an effective vaccine and for facilitation of an empirical choice of antibiotic treatment or prophylaxis for traveler's diarrhea in this area.
