During development, cell differentiation frequently occurs upon signaling from gradients of molecules, called morphogens. A simple paradigm to study morphogens is the Bicoid gradient, which determines antero-posterior patterning in fruit fly embryos. This transcription factor allows the rapid expression of its major target gene hunchback, in an anterior domain with a sharp boundary. Using the MS2 system to fluorescently tag RNA in living embryos, we were able to show that the ongoing transcription process at the hunchback promoter is bursty Surprisingly, it takes only 3 minutes, from the first hints of transcription at the anterior to reach steady state with the setting of the sharp expression border in the middle of the embryo. To better understand the role of transcription factors other than Bicoid in this process, I used a two-pronged strategy involving synthetic MS2 reporters combined with the analysis of the hunchback MS2 reporter in various mutant backgrounds. The synthetic reporter approach, indicate that Bicoid is able to activate transcription on its own when bound to the promoter but in a stochastic manner. The binding of Hunchback to the Bicoid-dependent promoter reduces this stochasticity while Caudal might act as a posterior repressor gradient. Altogether, this work provide a new light on the mechanisms insuring a precise transcriptional response downstream of Bicoid.

Developmental pattern formation is orchestrated by diffusible signaling molecules, termed morphogens, that form gradients from which cells can determine positionally appropriate fates. Stochasticity in morphogen binding, signal transduction, and gene expression create local cell-to-cell variability in the readout of morphogen gradients. However, little is known about the actual levels of noise in morphogen gradient responses, or the mechanisms that might control it. To investigate this, I quantified the transcriptional activity noise, protein expression noise, and protein half-life of optomotor blind (omb), one of the downstream targets of the morphogen Dpp in the Drosophila larval wing imaginal disc. Using combined fluorescence in situ hybridization (FISH) with intronic probes, immunofluorescence, image segmentation and image analysis, I observed a very high level of transcriptional variability characterized by coefficients of variation (CV) as high as ~110%, in the cells in which omb plays a central role in specifying the location of wing vein primordium L5. However, the half-life of the Omb protein was found to be very long, ~ 6 hours, which would be expected to provide significant temporal filtering of the transcriptional noise. I showed that the reduction in noise from transcript to protein is sufficient to account for the precision of the positional information that patterns vein L5. I also investigated why the positioning of vein L5 is remarkably robust to genetic manipulation that change the shape of the Dpp morphogen gradient. I observed that patters of Dpp signaling and Omb expression are not constant during larval development, but change continuously, and not always in concert with each other. By taking into account the long half-life of Omb it was possible to build a model that explains both these movements and the remarkable robustness of L5 patterning to changes in Dpp gradient shape.

Gradients and Tissue Patterning, Volume 137 in the Current Topics in Developmental Biology series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of timely topics. Each chapter is written by an international board of authors.

Signalling by morphogens such as the Hedgehog family, Notch, Wingless/Wnt and various growth factors is essential during embryogenesis. The establishment of concentration gradients of these morphogens plays a key role during developmental patterning in all multicellular organisms, assuring that distinct cell/tissue types and organs appear at the right place in the right time during embryogenesis. Regulation of morphogen synthesis, trafficking and diffusion are all known to play a part in setting up these gradients, and a complex web of signaling mechanisms ensures that specific responses occur at the correct threshold concentration in the recipient cells whose fate depends on these morphogens.

This topical volume in the respected Encyclopedia series is the first in many years to bring together all important aspects of developmental biology in one source, from morphogenesis and organogenesis, via epigenetic regulation of gene expression to evolutionary developmental biology. The editor-in-chief has assembled an outstanding team of contributors to review these topics, creating an authoritative work for many years to come. The result is a unique, top-level reference in developmental biology for researchers, students and professionals alike.

The genetic, molecular, and cellular mechanisms of neural development are essential for understanding evolution and disorders of neural systems. Recent advances in genetic, molecular, and cell biological methods have generated a massive increase in new information, but there is a paucity of comprehensive and up-to-date syntheses, references, and historical perspectives on this important subject. The Comprehensive Developmental Neuroscience series is designed to fill this gap, offering the most thorough coverage of this field on the market today and addressing all aspects of how the nervous system and its components develop. Particular attention is paid to the effects of abnormal development and on new psychiatric/neurological treatments being developed based on our increased understanding of developmental mechanisms. Each volume in the series consists of review style articles that average 15-20pp and feature numerous illustrations and full references. Volume 1 offers 48 high level articles devoted mainly to patterning and cell type specification in the developing central and peripheral nervous systems. Series offers 144 articles for 2904 full color pages addressing ways in which the nervous system and its components develop Features leading experts in various subfields as Section Editors and article Authors All articles peer reviewed by Section Editors to ensure accuracy, thoroughness, and scholarship Volume 1 sections include coverage of mechanisms which: control regional specification, regulate proliferation of neuronal progenitors and control differentiation and survival of specific neuronal subtypes, and controlling development of non-neural cells