M Affolter

..The requirements for tkv in dorsal closure, visceral mesoderm and trachea development assign novel functions to dpp or a closely related member of the TGF beta superfamily...

..Additional proteins binding either to the FGFRs, to Dof, or to Csw appear to be crucial for a chemotactic response...

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..We demonstrate that this is unlikely to be due to insulator bypass. The transvection effects described here may provide insight into the role that boundary element pairing plays in enhancer blocking both in cis and in trans...

..We also discuss the similarities and differences between flies and vertebrates in branched organ formation that are becoming apparent from these studies...

..Recent experiments suggest that cell competition and cell rearrangements might be conserved key features in branch formation and might be controlled by local cell signalling...

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..It remains to be seen whether similar molecular mechanisms operate in the nucleus in vertebrate systems...

..Continued efforts to elucidate the role of DPP in D. melanogaster is likely to shed light on this fundamental question in the near future...

..These new findings raise the interesting possibility that this repressive mode of action is shared by many or most developmental signaling pathways...

..In the latest issue of Cell Stem Cell, Singh et al. (2007) demonstrate that, in the adult fly, epithelial cells exist that are neither in niches nor in small numbers, divide at high rates, and are multipotent...

..2008) provides individual specificities for nearly all Drosophila and mouse homeodomains, key DNA-binding domains in many transcription factors. The data underscore the complexity of determining target specificities in vivo...

..It is required to control the dorsal expression of the BNL ligand; in addition, the DPP signal recruits groups of dorsal and ventral tracheal cells and programs them to migrate in dorsal and ventral directions...

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..The shn protein might therefore act as a nuclear target in the dpp signaling pathway directly regulating the expression of dpp-responsive genes...

..More than 30 genes have been identified and ordered into sequential steps controlling branching morphogenesis. These studies have revealed a number of important principles that might be conserved in other systems...

..The existence of several Shn-like proteins in vertebrates and the observation that Brk functions in BMP signalling in Xenopus indicates that a similar regulatory cascade may be conserved in higher organisms...

..Hence, each of the three characterized enhancers constitutes a molecular link between a specific territory induced by a morphogen signal and the localized expression of a gene required for the final differentiation of this territory...

..We discuss our findings in the light of the recent findings that RTKs generate a generic signal that is interpreted in responding cells according to their developmental history...

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..We propose that DSRF acts at a key step between regulatory genes that define the early positional values in the developing wing disc and the subsequent localized expression of intervein-specific structural genes...

..It selectively binds to the same sites as a longer Antp polypeptide and a full-length fushi tarazu (ftz) protein. Therefore, the homeodomain represents the DNA-binding domain of the homeotic proteins...

..Our results illustrate how a tissue-specific response to DPP can be generated through synergistic effects on an enhancer carrying both DPP- and HOX-responsive sequences...

..The DNA binding properties of the Antp HD and prokaryotic DNA binding domains that share a helix-turn-helix motif are compared...

..We suggest that ftz protein acts in combination with germ layer-restricted transcription factors directly and positively to regulate the transcription of its own gene...

..Isolated homeodomains bind with high affinity to specific DNA sequences. Thus, the structure-function relationship is highly conserved in evolution...

..Dof is needed in these cells for activation of the MAPK cascade via FGF signaling, but not for activation via other RTK ligands. Dof therefore appears to be committed exclusively to FGFR-mediated signal transduction...

..Together, our data suggest that these two proteins are involved in a common regulatory pathway and highlight possible interactions between Pc-G-mediated silencing and DNA replication in Drosophila...

..It has been demonstrated that chimeric peptide molecules encompassing pAntp are also captured by cultured neurons and conveyed to their nuclei. This may be of enormous interest for the internalization of drugs...

..These findings provide a hitherto unknown and interesting link between combinatorial inputs of transcription factors, cell-specific ligand expression and organ morphogenesis...

..These three points of contact allowed us to propose a crude orientation of the ftz HD within the protein-DNA complex. We find that the ftz HD and the Antp HD peptides contact DNA in a similar way...

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..Thus, the DSRF gene might play a role in the proper formation and maintenance of the trachea...

..We also identified a Sulfotransferase and a Multiple Inositol Polyphosphate phosphatase that are strongly upregulated in tracheal cells and discuss their possible involvement in tracheal development...

..Branching is controlled by several signaling pathways, but the molecular consequences of these pathways in the responding cells are poorly understood...

..Our study suggests that MAGUK proteins might play important roles during AJ remodeling in epithelial morphogenesis...

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..Ras and the Mapk pathway are also needed for Egf-regulated cell division/survival, but Pointed is dispensable...

..Bnl/FGF signaling affects the formation of dynamic filopodia, possibly controlling cytoskeletal activity and motility as such, and Dpp controls cellular functions allowing branch morphogenesis and outgrowth...

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..Clearly, both striking similarities and important differences are apparent, but it might still be too early to conclude whether the former or the latter prevail...

..The transition from a highly flexible, completely unfolded conformation in the absence of DNA to a well-formed structure in the complex presents a very extreme case of the "coupling of binding and folding" phenomenon...

..The molecular similarities between these two cases is reviewed here...

..In the developing fly wing, graded distributions of the morphogens Decapentaplegic and Wingless are essential for tissue patterning, but when it comes to growth, evidence suggests that it may not be so...

..We try to link these in vivo studies and the movement of cells over two dimensional substrates and elaborate on important questions which remain to be addressed in the future...

..We also find that salm activity is down-regulated by its own product and by that of the Pax gene eyegone...

..Our results suggest that a similar structural role might be attributed to other ZP-domain proteins in the formation of different branched organs...

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..Thus Lab, and most probably other Hox proteins, selects different DNA sequences in regulating downstream target genes. These observations have implications with regard to the current model of Hox-binding selectivity...

..To identify the functions of COPI coatomer-mediated membrane trafficking in Drosophila development, we were aiming to create loss-of-function mutations in the gammaCOP gene, which encodes a subunit of the COPI coatomer complex...

..Five genes are expressed during oogenesis; two of them are transcribed in the follicular epithelium, but not in the germ line cells...

..The AE allows the identification of hitherto unknown direct Dpp targets and is functionally conserved in vertebrates...

..In this review, we describe recent progress in understanding cell rearrangements during epithelial tube remodelling and discuss several models that might account for the developmental control of the spatial dynamics of AJs...

..We discuss the diversity of morphogenetic mechanisms that contribute to vessel assembly, angiogenic sprouting and tube formation in different blood vessels and how some of these complex cell behaviors are regulated by molecular pathways...

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..Three of the mutants were mapped to either the Mhc or the stam complementation groups. Further experiments confirmed that these genes are required for cell migration in the tracheal air sac primordium...

..Together, our results provide the molecular framework for a mechanism by which the extracellular Dpp/BMP morphogen establishes a finely tuned, graded read-out of transcriptional repression...

..The ligand of the FGF receptor Heartless, which is involved in mesoderm movement, has now been isolated and shown to be a link between a morphogen gradient and cell behavior...

..The second regulatory sequence is sufficient to drive correct early embryonic expression of ceh-13. Interestingly, this enhancer fragment acts as a response element of the Wnt/WG signaling pathway in Drosophila embryos...

..Toward that end, we have determined the crystal structure of the antagonist Noggin bound to BMP-7...

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..The scaffold of Noggin contains a cystine (the oxidized form of cysteine) knot topology similar to that of BMPs; thus, ligand and antagonist seem to have evolved from a common ancestral gene...

..We compare and contrast these insights with our current understanding of pathways controlling chemotactic movements in more-complex multicellular developmental contexts...