Research Group Prof. Dr. Manfred Frasch

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Patterning and Organogenesis in the Drosophila mesoderm

Our lab is studying the processes of mesoderm patterning and mesodermal tissue development in Drosophila. Genetic and molecular studies aim to define the identities and functions of regulatory molecules that spatially subdivide the mesodermal cell layer and determine the primordial cells of the heart, skeletal, and visceral musculatures at defined locations in the early embryo. We are also interested in processes of cell migration and tissue morphogenesis that are important for normal muscle and heart development.

Combinatorial signals and transcriptional inputs during progenitor specification

We have shown that several of the identified mesoderm patterning processes involve synergistic activities of mesoderm-specific transcription factors and signaling molecules that are secreted from the ectoderm. For example, the mesodermally-expressed homeobox gene tinman cooperates with the ectodermally-secreted factor Dpp, a TGF-b molecule of the BMP family, to subdivide the mesoderm into a ventral and a dorsal portion and to determine dorsal mesodermal derivatives. Molecularly, this process involves the binding of Dpp-activated signal transducers (the Smad proteins Mad and Medea), together with the Tinman protein itself, to target enhancers of genes such as tinman, bagpipe, and even-skipped, which results in their spatially-restricted activation in the dorsal mesoderm. Other spatial cues such as Wingless, Hedgehog, and the forkhead domain protein Sloppy Paired provide additional inputs for subdividing the dorsal mesoderm into heart, gut muscle, and somatic muscle primordia. We are interested in finding out how these combinatorial activities cooperate at the molecular level to activate or repress developmental control genes in defined groups of cells. Moreover, we study how some of these control genes (e.g., the Dorsocross and org-1 T-box genes, the homeobox gene bagpipe, the forkhead domain encoding gene biniou, and others) ultimately specify cell fates of the cardiac, visceral, and skeletal musculatures. We also perform genetic and genomic screens to identify new targets genes of these control genes as well as new regulators of mesodermal tissue development.

Example: Integrated signaling and transcriptional inputs regulate the transdifferentiation of heart-associated muscles during metamorphosis. The anterior, syncytial alary muscles (left) dedifferentiate into mononuclear myoblasts (middle), which become muscle founder cells that upon myoblast fusion redifferentiate into the ventral longitudinal muscles that are associated with the adult heart (right). This process is controlled by the combinatorial activities of the cell type-specific transcriptional regulators Org-1 and Tup, the region-specific Hox factor Ubx, as well as FGF- and ecdysone signals (Schaub, März, Reim & Frasch, 2015).

Cell migration and muscle morphogenesis

Prior to their fusion with fusion-competent myoblasts, the founder cells of the somatic muscles and particularly the longitudinal gut muscles undergo precisely-controlled cell migrations. We are currently aiming to identify some of the guidance cues and other mechanisms that are essential for the migration of these cells to their destinations.

Evolutionary conservation of muscle and heart development

Importantly, most of the identified regulators and pathways in mesoderm development are evolutionarily conserved. It appears that mesoderm patterning, muscle development, and cardiogenesis in insect and vertebrate embryos involve many closely related mechanisms. Therefore, Drosophila can serve as an excellent model system for developmental processes of the heart, skeletal and gut muscles, as well as organogenesis of other internal organs, in vertebrate embryos.We are taking further advantage of evolutionary conservation in muscle development by screening for genes that are required for somatic muscle development in the beetle Tribolium, which provides the benefit of systemic RNA interference. Within the DFG-funded iBeetle consortium, a genome-wide RNAi screen is being performed, in which muscle-GFP-marked embryos are screened for muscle defects upon pupal double-stranded RNA injections. The functions of newly-identified regulatory genes and their orthologs are being analyzed both in Tribolium and in Drosophila.

Members

Jakob Bartle (Master student)
Daniel Pfeifer (PhD student)
Claudia Obermeier (BTA)
Helena Pissarek (Master student)
Adrian Rieck (Master student)
Christoph Schaub (Post doc)
Dorothea Schultheis (PhD student)
Jochen Trauner (Teaching and scientific staff)
Matthias Weißkopf (PhD student)

Alumni


Name

Position

Period

Previous Institution

Current Position

E-mail

Cord Dohrmann

Diploma Student

1990-1991

Tübingen University, Germany

Chief Scientific Officer
Evotec AG, Hamburg

 

Natalia Azpiazu

Graduate Student

1991-1994

Tübingen University, Germany

Group Leader
CBM/Madrid University, Spain

Nazpiazu(at)cbm.uam.es

Polonca Küssel

Graduate Student

1990-1995

Tübingen University, Germany

Director, Head of Europe
Global Clinical Operations, Teva Pharmaceuticals

 

Xiaolei Xu

Graduate Student

1994-1999

Fudan University, Shanghai

Associate Professor
Mayo Clinic, Rochester MI

Xu.Xiaolei(at)mayo.edu

Stefan Knirr

Postdoc

1997-2000

Marburg University, Germany

Patent Attorney
Henry M. Feiereisen, LLC, New York, NY

 

Stephane Zaffran

Postdoc

1997-2001

Marseille University, France

Directeur de recherche
Inserm UMR 910
Faculte de Medecine La Timone, Marseilles, FR

Stephane.Zaffran(at)univmed.fr

Hsiu-Hsiang Lee

Graduate Student
Postdoc

1997-2003
2003-2004

National Taiwan University

Assistant Professor
National Taiwan University, Taipeh

hsiu.lee01(at)gmail.com

Patrick Lo

Postdoc
Associate

1994-2007

Columbia University, NY

Senior Editor
BioTechniques

patrick.lo(at)informausa.com

Hideyuki Nagaso

Postdoc

2001-2007

Hokkaido University, JP

Pharma business
Hokkaido, JP

 

Ingolf Reim

Postdoc

2001-2007

Humboldt University, Berlin

Group Leader
University of Erlangen-Nuremberg
Developmental Biology

Ireim(at)biologie.uni-erlangen.de

Afshan Ismat

Graduate Student

2003-2007

Rutgers University, NJ

Assistant Professor, University of St. Thomas, St. Paul, MN

afshan.ismat(at)stthomas.edu

Dominik Müller

Postdoc

2005-2009

Hohenheim University, Stuttgart

High School teacher
Helene-Lang-Gymnasium Fürth

domuelle(at)biologie.uni-erlangen.de

Katharina Seitz

Diploma Student

2008

University of Erlangen-Nuremberg

k.kathl(at)web.de

Hong Jin

Graduate Student

2008-2012

Shanghai Medical College of Fudan University

Post Doc, Department of Biochemistry & Molecular Biology,
University of Calgary, Canada

 

Publications