Mutant of the Month

Credit: Alexander Schier

For this month's MoM, the name says it all. Dubbed one-eyed pinhead (oep), this zebrafish mutant lacks ventral forebrain structures, resulting in fusion of the eye fields at the midline. These characteristic cyclopic features are shared by a class of zebrafish mutants identified through the large-scale mutagenesis screens conducted in Boston and Tübingen in the early 1990s. oep encodes a protein with similarity to epidermal growth factor (EGF), leading to the initial speculation that Oep functioned as a permissive EGF-related ligand. Alex Schier and colleagues subsequently found, however, that mutants lacking both maternal and zygotic oep function have the same phenotype as double mutants for cyclops and squint, two members of the Nodal subclass of transforming growth factor (TGF) β–related ligands. Further investigation showed that Oep indeed acts as an essential extracellular cofactor for Nodal-related signals, with important roles during germ layer formation, ventral forebrain induction and left-right axis specification. Defects associated with mutations in human oep homologs include heterotaxia and ventral forebrain anomalies, highlighting the conserved role of the so-called EGF-CFC family in mediating Nodal-related signaling in humans. KV

The big three and neglected diseases

The World Economic Forum held this past month in Davos, Switzerland, reviewed efforts to address the 'big three' infectious diseases: HIV/AIDS, malaria and tuberculosis. Notably, representatives of major foundations that have in recent years focused global efforts on these public health threats (including the Bill and Melinda Gates Foundation; the Global Fund to Fight AIDS, TB, and Malaria; the Joint UN Programme on HIV/AIDS; and Stop Tuberculosis) spoke on their efforts and made pledges and calls for increased funding. Shortly after this summit, the focus shifted away from these big three epidemics at the Malaria and Neglected Tropical Disease Quick-Impact Initiative Meeting, held January 30–31, 2006, in Stockholm, Sweden. Here, a mixture of politicians, scientists, drug company representatives and public health officials came together to develop strategies for control of these epidemics in the context of other local epidemics and, in particular, the widespread but too-often-neglected tropical diseases. In an article published this past month, Jeffrey Sachs and colleagues present an analysis of the impact of incorporating interventions for 13 neglected tropical disease (including schistosomiasis, filariasis, onchocerciasis and trachoma) within current programs for HIV/AIDS, tuberculosis and malaria (PLoS Med. 3, e102; 2006). The study surveys evidence, for example, that parasitic worms contribute to susceptibility and progression rates of these big three infectious diseases. The authors also provide helpful updated global estimates of burden of disease for these neglected diseases, giving estimates significantly higher than from recent World Health Reports. The article also points out the importance of considering coinfection with multiple parasites, highlighting the importance of understanding factors predisposing to risk of infection as well as associations between these infections. OB

WTO rules against EU biotech ban

As Nature Genetics went to press, a preliminary ruling of the World Trade Organization found that the European Union (EU) violated international trade rules in its 6-year moratorium on the importation of genetically modified organisms (GMOs). The ruling also apparently condemns the national 'safeguards' on GMOs that have been imposed by Germany, France, Austria and Greece since the lifting of the EU moratorium in 2004. The original complaint, lodged by the United States, Canada and Argentina in 2003, claimed that the effective EU ban on GMOs was not scientifically justified and amounted to an unfair trade barrier. Commentators argue that the strength of the market for genetically modified crops is still not likely to improve in Europe, given the grassroots opposition to them, although the strong signal sent by the WTO may influence the policies of other countries, including China, India, Russia, Japan, Indonesia and Mexico, each of which has its own rules mandating labeling and traceability of genetically modified ingredients. Ironically, the dispute has the United States in the position of relying on an international organization while members of the EU make claims for their sovereign right to restrict GMOs in accordance with the wishes of their people, a state of affairs that is typically the other way around. The full 1,112-page report is to be released in several weeks, pending revision. AP

Touching Base written by Orli Bahcall, Alan Packer and Kyle Vogan.