Type IV collagens regulate BMP signalling in Drosophila

Dorsal-ventral patterning in vertebrate and invertebrate embryos is mediated by a conserved system of secreted proteins that establishes a bone morphogenetic protein (BMP) gradient. Although the Drosophila embryonic Decapentaplegic (Dpp) gradient has served as a model to understand how morphogen gradients are established, no role for the extracellular matrix has been previously described. Here we show that type IV collagen extracellular matrix proteins bind Dpp and regulate its signalling in both the Drosophila embryo and ovary. We provide evidence that the interaction between Dpp and type IV collagen augments Dpp signalling in the embryo by promoting gradient formation, yet it restricts the signalling range in the ovary through sequestration of the Dpp ligand. Together, these results identify a critical function of type IV collagens in modulating Dpp in the extracellular space during Drosophila development. On the basis of our findings that human type IV collagen binds BMP4, we predict that this role of type IV collagens will be conserved.     

Temporal dissection of p53 function in vitro and in vivo

To investigate the functions of the p53 tumor suppressor, we created a new knock-in gene replacement mouse model in which the endogenous Trp53 gene is substituted by one encoding p53ER(TAM), a p53 fusion protein whose function is completely dependent on ectopic provision of 4-hydroxytamoxifen. We show here that both tissues in vivo and cells in vitro derived from such mice can be rapidly toggled between wild-type and p53 knockout states. Using this rapid perturbation model, we define the kinetics, dependence, persistence and reversibility of p53-mediated responses to DNA damage in tissues in vivo and to activation of the Ras oncoprotein and stress in vitro. This is the first example to our knowledge of a new class of genetic model that allows the specific, rapid and reversible perturbation of the function of a single endogenous gene in vivo.     

Post-Normal Science, the Precautionary Principle and the Ethics of Integrity

Present laws and regulations even in democratic countries are not sufficient to prevent the grave environmental threats we face. Further, even environmental ethics, when they remain anthropocentric cannot propose a better approach. I argue that, taking in considerations the precautionary principle, and adopting the perspective of post-normal science, the ethics of integrity suggest a better way to reduce ecological threats and promote the human good globally. This revised version was published online in July 2006 with corrections to the Cover Date.     

Acoustic ecology of an anuran assemblage in the arid Caatinga of northeastern Brazil

Differences in advertisement calls and calling sites are important mechanisms that regulate interactions in anuran assemblages. Individuals might have preferences for ranges of acoustic parameters and calling sites that reduce overlap and ensure coexistence. Herein, acoustic and ecological data were used to investigate the relationships among 12 anurans that co-occur in temporary ponds in the Caatinga, Cabaceiras municipality, Paraíba state, Brazil. Anurans exhibited calling activity correlated with rainfall, but were also spatially dispersed. High overlap levels in calling microhabitats and acoustic parameters were observed, especially among pairs of closely related species. Analysis of null models showed a lack of structure in the spatial and acoustic niche, indicating the lack of detected competition. Results suggest that the calling activity of the species is strongly influenced by rainfall, moreover, the temporal partition appears to ensure coexistence. Finally, strong historical effects were detected in Leiuperinae, Leptodactylidae and in the partition Hylidae–Leptodactyliformes.     

Regulation of DNA methylation of Rasgrf1.

In mammals, DNA is methylated at cytosines within CpG dinucleotides. Properly regulated methylation is crucial for normal development. Inappropriate methylation may contribute to tumorigenesis by silencing tumor-suppressor genes or by activating growth-stimulating genes. Although many genes have been identified that acquire methylation and whose expression is methylation-sensitive, little is known about how DNA methylation is controlled. We have identified a DNA sequence that regulates establishment of DNA methylation in the male germ line at Rasgrf1. In mice, the imprinted Rasgrf1 locus is methylated on the paternal allele within a differentially methylated domain (DMD) 30 kbp 5' of the promoter. Expression is exclusively from the paternal allele in neonatal brain. Methylation is regulated by a repeated sequence, consisting of a 41-mer repeated 40 times, found immediately 3' of the DMD. This sequence is present in organisms in which Rasgrf1 is imprinted. In addition, DMD methylation is required for imprinted Rasgrf1 expression. Together the DMD and repeat element constitute a binary switch that regulates imprinting at the locus.