Research Report 2010 - MDC

Structure of the GroupSalim SeyfriedGroup LeaderDr. Salim SeyfriedScientistsDr. Nana Bit-Avragim*Dr. Nicole Hellwig*Graduate StudentsElena Cibrián-Uhalte*David Hava*Cécile OttenFlorian Priller*Marc RenzStefan Rohr*Sabine Seipold*Justus Veerkamp*Jingjing ZhangTechnical AssistantsNicole Cornitius*Nicole Dittberner*Jana Richter*part of the periodreportedEpithelial Morphogenesis andZebrafish GeneticsVertebrate organs are derived from epithelial sheets that undergo complex morphogenetictransformations. The molecular mechanisms that regulate the polarization of epithelial cells arecrucial in this process. We have studied the early zebrafish heart, a relatively simple organ comparedwith its mammalian counterpart, to better understand the link between cell polarity, epithelialmorphogenesis and signaling events that instruct the assembly of a heart tube. We would like tounderstand: How do the different protein complexes that establish cell polarity interact with eachother? How is cell polarity regulated within epithelial sheets during morphogenesis of tissues andorgans? What are the signals that regulate cell polarity and epithelial morphogenesis duringcardiogenesis? Our long-term interest is to understand how the cellular mechanisms controlling cellpolarity shape our own bodies. Insight from developmental genetics and cell biological approachesdeployed within our research group are being used in collaboration with clinical research teams toidentify genes responsible for human congenital heart disease.Asymmetric behaviors of myocardial cells drivezebrafish heart tube formationStefan Rohr, Cécile OttenMany vertebrate organs are derived from monolayeredepithelia that undergo morphogenetic changes toacquire their final shapes. Little is known about the tissuemovements or cellular dynamics underlying earlycardiac morphogenesis. In particular, the process bywhich the flat heart field is transformed into a lineartube was largely unexplored in vertebrates. In a recentstudy, we described a completely unexpected tissuemorphogenetic process by which the nascent hearttube is generated in the zebrafish embryo. We discoveredthat asymmetric involution of the myocardialepithelium from the right side of the heart field initiatesa complex tissue inversion which creates the ventralfloor of the primary heart tube whereas myocardial cellsderived from the left side of the heart field contributeexclusively to the future dorsal roof of this organ (Fig. 1).Intriguingly, asymmetric left-right gene expression withinthe myocardium correlates with asymmetric tissuemorphogenesis and disruption of left-right gene expressioncauses randomized myocardial tissue involution.Our results demonstrated that asymmetric morphogeneticmovements of the two bilateral myocardial cellpopulations generate different dorso-ventral regions ofthe zebrafish heart tube. Failure to generate a hearttube did not affect the acquisition of atrial versus ventricularcardiac cell shapes. Therefore, establishment ofbasic cardiac cell shapes precedes cardiac function.Together, these results provide a framework for the integrationof single cell behaviors during the formation ofthe zebrafish primary heart tube.Divergent polarization mechanisms duringvertebrate epithelial development mediated bythe Crumbs complex protein Nagie oko/Mpp5Nana Bit-Avragim, Nicole Hellwig, Franziska Rudolph(in collaboration with Chantilly Munson, Didier Y.S.Stainier, University of California, San Francisco)Nagie oko (Nok)/Mpp5 is a member of the conservedStardust/Pals1/Mpp5 family of MAGUK proteins and anintegral component of the apical Crumbs-Patj-Par6-aPKCprotein complex of cell polarity regulators. We performeda functional characterization of its different protein-pro-18 Cardiovascular and Metabolic Disease Research