Proceedings: consideration of genetics in the design of induced pluripotent stem cell-based models of complex disease.

The goal of exploiting induced pluripotent stem cell (iPSC) technology for the discovery of new mechanisms and treatments of disease is being pursued by many laboratories, and analyses of rare monogenic diseases have already provided ample evidence that this approach has merit. Considering the enormous medical burden imposed by common chronic diseases, successful implementation of iPSC-based models has the potential for major impact on these diseases as well. Since common diseases represent complex traits with varying genetic and environmental contributions to disease manifestation, the use of iPSC technology poses unique challenges.

Chimeric primates: embryonic stem cells need not apply.

In this issue, Tachibana et al. report the generation of the first chimeras from a nonhuman primate, the rhesus monkey. Unlike mice, rhesus chimeras fail to form when embryonic stem cells are injected into blastocysts.

Kidney development in the absence of Gdnf and Spry1 requires Fgf10.

GDNF signaling through the Ret receptor tyrosine kinase (RTK) is required for ureteric bud (UB) branching morphogenesis during kidney development in mice and humans. Furthermore, many other mutant genes that cause renal agenesis exert their effects via the GDNF/RET pathway. Therefore, RET signaling is believed to play a central role in renal organogenesis.

A Cre transgene active in developing endodermal organs, heart, limb, and extra-ocular muscle.

Cre-mediated recombination, a method widely used in mice for tissue-specific inactivation of endogenous genes or activation of transgenes, is critically dependent on the availability of mouse lines in which Cre recombinase functions in the tissue of interest or its progenitors. Here we describe a transgenic mouse line, Osr1-cre, in which Cre is active from embryonic day (E)11.5 in a few specific tissues.

FGF8 is required for cell survival at distinct stages of nephrogenesis and for regulation of gene expression in nascent nephrons.

During kidney morphogenesis, the formation of nephrons begins when mesenchymal nephron progenitor cells aggregate and transform into epithelial vesicles that elongate and assume an S-shape. Cells in different regions of the S-shaped body subsequently differentiate into the morphologically and functionally distinct segments of the mature nephron. Here, we have used an allelic series of mutations to determine the role of the secreted signaling molecule FGF8 in nephrogenesis.

SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site.

Kidney development occurs in a stereotypic position along the body axis. It begins when a single ureteric bud emerges from the nephric duct in response to GDNF secreted by the adjacent nephrogenic mesenchyme. Posterior restriction of Gdnf expression is considered critical for correct positioning of ureteric bud development.