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Abstracts - Society for Developmental Biology

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19<br />

Dominguez-Castellano, Maria; Garelli, Andres; Gontijo, Alisson; Miguela, Veronica; Caparros, Esther (Inst Neuroci<br />

Alicante, Spain)<br />

Animal size is amazingly constant within species and this constancy is even more striking when we consider the<br />

coincidence in size of the left and right sides of bilaterian organisms. To attain such precision, growing organs must be<br />

capable to sense and communicate their growth to other organs in the organism and to have flexibility to adjust their<br />

growth programmes and the timing of maturation to repair disturbances during ontogeny. How they do so remains a<br />

mystery. We have addressed this issue in the imaginal discs of the fruit fly Drosophila melanogaster, which are known to<br />

have a remarkable flexibility to regulate their size, particularly when they suffer lesions. I will present the findings that<br />

growing imaginal discs produce, and secrete to the hemolymph, a novel insulin/relaxin-like peptide that mediates the<br />

plasticity of growth and maturation that ensures the proper final size,proportions, and the symmetry between the two sides.<br />

Program/Abstract # 58<br />

!): Trying to fathom the mechanisms of planar cell polarity.<br />

Lawrence, Peter, University of Cambridge, United Kingdom<br />

In the past 100 years or more of developmental biology, the significance of vectorial in<strong>for</strong>mation has often been<br />

overlooked, yet an individual cell cannot contribute properly to building an animal without in<strong>for</strong>mation both of its position<br />

(that relates to its identity) but also its orientation within the whole. For example, it needs to know which orientation to<br />

divide, which route to move, which direction to send an axon or outgrowth etc. These properties of polarity have lately<br />

become known as planar cell polarity (PCP). I first came across PCP as a graduate student exactly 50 years ago. After<br />

having done some work on this problem <strong>for</strong> a few years, I then dropped it until about 1995 when I returned to it 100%.<br />

Since then I have been collaborating with José Casal (Cambridge, UK) and Gary Struhl (Columbia, NY) to research the<br />

mechanism of PCP using mostly genetic methods (particularly mosaics) with Drosophila. We are unconventional in that<br />

we are all 3 doing only research and all of us are aged over 50. I will tell the story of what we have discovered and how we<br />

have approached this deep and fascinating problem. Our main findings have been concerned with the functions of three<br />

cadherin proteins, Flamingo (aka Starry Night), Dachsous, and Fat. The <strong>for</strong>mer protein works with Frizzled and Van Gogh<br />

within one pathway and the latter two work together with Four-jointed and Dachs in a second independent pathway. Both<br />

pathways help determine the polarity of cells in the epidermis. In both these pathways, polarity in<strong>for</strong>mation is transferred<br />

from cell to cell via cadherin proteins that constitute molecular bridges. These processes appear to be conserved to<br />

vertebrates.<br />

Program/Abstract # 59<br />

Tissue specific analysis of chromatin identifies temporal enhancer activity in Drosophila mesoderm development<br />

Zinzen, Robert P.; Bonn, Stefan; Girardot, Charles; Perez-Gonzalez, Alexis; Delhomme, Nicolas; Wilczynski, Bartek;<br />

Riddell, Andrew; Furlong, Eileen E.E., EMBL, Heidelberg, Germany<br />

Epigenetic histone modifications and genome-wide binding profiles of general transcription factors can serve as reliable,<br />

global read-outs <strong>for</strong> the regulatory state of genes and enhancers. A challenge in a developmental context, however, has<br />

been that such features are generally employed throughout the developing embryo. There<strong>for</strong>e, whole-embryo studies can<br />

only yield non-specific data from multiple tissues and cell types where any in<strong>for</strong>mative signatures are diluted and<br />

contradicting data from diverse tissues is superimposed. We have developed a new method to batch-isolate tissue-specific<br />

chromatin followed by immunoprecipitation (BiTS-ChIP) and have applied this method to the developing Drosophila<br />

embryo by extracting mesoderm-specific signatures <strong>for</strong> histone modifications and Pol II positioning. The tissue-specific<br />

data is of high sensitivity and specificity and reveals that enhancers exhibit heterogeneous chromatin/Pol II states and that<br />

specific states are highly correlated with spatio-temporal enhancer activity. Though H3K4me1 enrichment generally marks<br />

enhancers, it provides no in<strong>for</strong>mation on the activity state of regulatory regions; however, other features such as H3K27ac,<br />

H3K79me3 and especially Pol II enrichment clearly mark active enhancers with temporal precision. In a machine-learning<br />

approach based on the uncovered enhancer signatures, we were able to faithfully identify new enhancers that direct spatiotemporal<br />

activity as predicted. Such cell type-specific data can there<strong>for</strong>e identify enhancers in active use during<br />

development, which will be instrumental in deciphering cis-regulatory networks. Furthermore, our BiTS method should be<br />

widely applicable and easily adaptable toother tissues and animals.<br />

Program/Abstract # 60<br />

Regulatory Genomics in Drosophila<br />

Stark, Alex, IMP-Vienna, Austria<br />

During animal development, the transcription of genes is tightly controlled in a temporal and spatial fashion by cisregulatory<br />

modules (CRMs) or enhancers. Enhancers are DNA elements that contain sequence motifs <strong>for</strong> specific

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