NETWORK
 \  NETWORK
Miguel Torres Sánchez (Coordinator)

CNIC

The Torres group is developing projects towards understanding the cellular basis of early cardiac

morphogenesis and its regulation by Transcription Factors of the homeodomain family. The heart is the first organ to acquire its function during embryonic development and has a vital role in pumping nutrients/oxygen. In the early vertebrate embryo, the heart is initially a single primitive contractile cardiac tube. In mammals, it originates from a horseshoe-shaped flat cardiac crescent continuous across the midline that merges at the midline to form a tube. While

in recent years significant progress has been made in our understanding of the gene regulatory logic that controls early heart development, approaches toward a comprehensive framework of the cell behaviors underlying the formation of the primitive heart tube from the cardiac crescent are still missing. Cardiac congenital defects are very prevalent (1% of live born) and mostly consist in defects of the complex morphogenetic events involved in cardiac formation. While there is extensive information about the genetic basis of these defects, there is no understanding of the mechanism linking gene function with the morphogenetic events. The group is combining genetic approaches for in vivo labeling of individual cardiac progenitor cells

with advanced time-lapse 3D microscopy techniques (2-photon and light sheet microscopy) and

embryo culture. Using these approaches, they are obtaining data on the cellular history of the early heart tube and accurate morphometric and dynamic maps of tissue movements and deformations during cardiac tube formation. These data will be used to produce digital descriptions of cardiac tube formation at cellular resolution and generate 4Dmaps of cellular behavior parameters.

Web

James Sharpe

Centro de Regulación Genómica

The Sharpe lab brings together an interdisciplinary team of scientists focusing on a particular complex system – development of the vertebrate limb. The group includes embryologists, computer scientists, imaging specialists and engineers. The group aims to capture the whole process of understanding, from novel approaches for data-capture (live time-lapse OPT imaging) to finite-element simulations of the growing 3D structure and computer models of the gene networks responsible for pattern formation across the organ. Using this interdisciplinary approach, the group has achieved a number of insights into limb development. They first addressed the mechanical basis for limb bud elongation, and by combining a 3D finite element model with quantitative data on shape changes and proliferation rates, they were able to disprove a 4-decades old dogma in the field that elongation is driven by spatially controlled tissue growth. The group has also worked on methods to accurately determine the developmental stage of a mouse limb bud, purely from morphometric analysis, and has used clonal analysis from the Torres lab to build a numerical description of tissue movements in 2D. More recently, they have built models of the gene regulatory networks within the growing tissue of the limb bud. In this way they have been able to propose that the digit pattern is achieved by a Turing reaction diffusion system which is modulated by the Hox genes and a spatial gradient of FGF signaling. The group has recently also sought the molecular players of the Turing network itself, and found that the Bmp and Wnt signaling pathways appear to be the major molecular components.

Web

Andrés Santos Lleó

Universidad Politécnica de Madrid

The Santos group has a relevant experience on image processing tools for understanding embryo
development. The understanding of the processes underlying embryo development from a single cell into a multicellular organism is a long-term goal of Developmental Biology
that is recently being feasible thanks to the availability of massive 3D +t complex data acquired with new microscopy technologies. But these large quantities of data require automated or semiautomated image processing methods to be possible. Current developments and challenges in biological image processing include algorithms for microscopy multiview fusion,
cell nucleus tracking for lineage reconstruction, cell segmentation, multidimensional image registration and gene expression atlases. These tools are to eventually produce in toto reconstruction of the embryo development combining the cell lineage tree with quantitative gene expression data in its spatiotemporal context. In collaboration with scientists from Institut de Neurobiology Alfred Fessard (CNRS, Gif-sur-Yvette, France) and from École Polytechnique (Palaiseau, France), our group has been working on several of the tools required:
·A wavelet multiview image fusion for Light-Sheet Fluorescence Microscopy to combine information from all available views into a single volume with improved overall contrast.
·A cell lineage reconstruction workflow for early stages of embryo development with dedicated
tracking and segmentation tools.
·A digital framework for the construction of gene expression atlases of embryogenesis based on image registration algorithms to combine information from different individuals

Web

Jorge Garcia Ojalvo

Universidad Pompeu Fabra
Jordi Garcia-Ojalvo obtained his PhD in statistical physics at the University of Barcelona in 1995. He did postdoctoral work at the Georgia Institute of Technology in Atlanta in 1996, working on laser dynamics, and at the Humboldt University of Berlin in 1998 as an Alexander von Humboldt Fellow, studying noise effects in excitable media. He was IGERT Visiting Professor at Cornell University in Ithaca, New York, in 2003, at which time he began working in the field of systems biology. In 2008 he became Full Professor at the Universitat Politecnica de Catalunya, where he had been teaching applied physics since 1991. He is Visiting Research Associate in Biology at the California Institute of Technology since 2006, and joined the Universitat Pompeu Fabra in October 2012.

research interest

The laboratory of Dynamical Systems Biology at Universitat Pompeu Fabra is interested in the dynamics of living systems, from unicellular organisms to human beings. We use dynamical phenomena to identify the molecular mechanisms of cellular processes, such as bacterial stress response, spatial self-organization in bacterial biofilms, pluripotency in stem cells, and the immune response to cytokine signaling. Using a combination of theoretical modeling and experimental tools such as time-lapse fluorescence microscopy and microfluidics, we investigate dynamical phenomena including biochemical pulses and oscillations, and study how multiple instances of these processes coexist inside the cell in a coordinated way. At a larger level of organization, we use conductance-based neural models to explain the emergence of collective rhythms in cortical networks. We also work on developing a global description of brain activity by means of mesoscopic neural-mass models, which allows us to link the structural properties of brain networks with their function.

Web

Jorge Ripoll Lorenzo

Universidad Carlos III de Madrid
The main activities of the Ripoll lab are oriented towards 3D in-vivo imaging, in particular:

  1. Development of novel microscopy approaches capable of fast and multispectral 3D imaging of developing organisms and organogenesis
  2. Development of numerical methods for 3D imaging accounting for fast movement and scattering.
  3. Inverse Problems dedicated to improving image resolution and quantification of live 3D+t data.

3D Time-lapse imaging, in particular 3D time-lapse imaging of fast processes such as the beating
zebrafish heart or single-cell tracking in living organisms is one of the main challenges that modern microscopy faces. In order to obtain high resolution 3D+t images one can either take advantage of periodic movements (as in a healthy beating heart) or must resort to using extremely fast 3D imaging approaches capable of producing a 3D stack in a time shorter than the typical movement. Ripoll ́s lab is working on both approaches, the latter being more generally applicable to all time-lapse development imaging, specifically those that deal with single cell tracking through a large volume such as a developing embryo or organ. Such approaches require the design and implementation of a specialized microscope (a multi-spectral SPIM with very fast scientific CMOS cameras and sample scanning independent of sample movement, currently setup at the UC3M, custom software for hardware control, and advanced solution to inverse problems, capable of rendering 3D images and handling extremely large amounts of data.

Web

Maria Angeles Ros Lasierra

Instituto de Biomedicina y Biotecnología de Cantabria (CSIC)
The Ros lab studies the molecular basis of morphogenesis: how the formation of a particular form or structure is genetically and molecularly controlled during vertebrate development. The group also pursues to uncover the origins of the developmental defects that lead to human malformations and other diseases. To achieve this task the group combines classical methods of experimental embryology with genetic and biochemical approaches and also more recently with modern genome-wide technologies. The experimental system they use is the developing mouse and chick embryos concentrating mainly, but not exclusively, in the limb. The group has contributed to the identification of the molecular basis of the signaling centers operating in the limb bud including i) the specification of the three proximo-distal segments typical of the tetrapod limb, ii) the formation and function of the apical ectodermal ridge, one major signaling center in the bud, and iii) the control of digit number and identity. Recently, searching to unravel the molecular basis of pentadactyly, the group characterized several murine models with oligo/polydactyly, two common human limb malformations. They found that the removal of Gli3 and 5’Hox genes resulted in severe polydactylous limbs of thin, short, and densely packed digital rays. These phenotypes were concordant with a Turing-type mechanism controlling digit patterning and Hox genes modulating its wavelength. They have also identified the crucial and redundant role played by Sp6 and Sp8, two transcription factors members of the Sp family, in the limb ectoderm. Compound mutations of Sp6 and Sp8 are a model of the Spli Hand/Foot Malformation Syndrome. Finally, by classical grafting experiments in chick embryos and taking advantage of the chicken strain ubiquitously expressing GFP we have shown the intrinsic behavior of the limb progenitor cells in limb proximo-distal patterning.

Web