Development Biology

BMP4 initiates human embryonic stem cell differentiation to trophoblast. Xu, R. -H. et al. Nature Biotechnol. 20, 1261–1264 (2002)

Although embryonic stem (ES) cells are well known for their controversial application in transplantation therapy, they are also important for understanding the development and function of different cell types. This paper shows that human ES cells can be induced to differentiate into trophoblast — which develops before the three embryonic germ layers — by bone morphogenetic protein 4. This result reinforces the value of human ES-cell research as mouse and human trophoblast are significantly different and mouse ES cells differentiate poorly into trophoblast.

Disease Genetics

A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish. Liu, S. et al. Development 129, 5839–5846 (2002)

Mice with the juvenile cystic kidney (jck) mutation are good models for the human disorder polycystic kidney disease (PKD). The authors have positionally cloned the jck mutation, which corresponds to a point mutation in the kinase-encoding gene Nek8. The role of Nek8 in PKD was confirmed by in vitro overexpression studies and the polycystic phenotype of zebrafish in which the Nek8 orthologue was inactivated using antisense oligonucleotides. Gene function can therefore be successfully investigated using comparative analyses.

Functional Genomics

Integrating interactome, phenome, and transcriptome mapping data for the C. elegans germline. Walhout, A. J. M. et al. Curr. Biol. 12, 1952–1958 (2002)

Gene clustering based on RNAi phenotypes of ovary-enriched genes in C. elegans. Piano, F. et al. Curr. Biol. 12, 1959–1964 (2002)

Integration of functional genomics approaches and protein–protein interaction data on a global scale provides an opportunity for the thorough testing of biological hypothesis. Such an integrative analysis has already been carried out in yeast, and now Walhout et al. have done a similar analysis for the Caenorhabditis elegans germline. They have combined a protein–protein interaction map (obtained from yeast two-hybrid data for 600 germline-expressed transcripts) with large-scale phenotypic analysis of germline-specific genes (based on RNA interference (RNAi) data from Piano et al.) and transcriptome profiling (obtained by clustering transcripts from several expression profiling experiments). They find that, in a quarter of germline interactions, both partners have RNAi phenotypes that are either embryonic lethal or masculinizing, indicating that these interactions might be most relevant for germline biology.