of the Max - MDC

Structure of the Group
Group Leader
Dr. Salim Abdelilah-Seyfried
Scientists
Dr. Nana Bit-Avragim*
Dr. Nicole Hellwig*
Graduate Students
Elena Cibrian-Uhalte
David Hava
Cecile Otten
Sabine Seipold*
Stefan Rohr
Technical Assistants
Jana Richter
Nicole Cornitius
* part of the period reported
Figure 1. Cell shape changes contribute to heart tube elongation.
(A-C) Schematic diagram of atrial (A, green) versus ventricular (V,
red) myocardial tissue expansion during heart tube elongation.
(D) Dorsal view onto the atrial heart field of a 32 hour old embryo.
Membrane red fluorescent protein expressed within myocardial cells
reveals shapes of atrial roof cells whereas green fluorescent protein
marks nuclei and part of the cytoskeleton. (E) Section along the
anterior-posterior axis of the developing heart tube marked by
expression of green fluorescent protein within myocardial cells. Red
line within inset diagram represents the level and orientation of the
section plane. (D, E) Atrial expansion is mainly driven by cuboidal
to squamous epithelial shape changes (white arrows) rather than by
cell proliferation.
Figure 2. Heart tube elongation requires the Na pump function.
(A) Expression of the myocardial marker cmlc2 in a wild type
embryo marks the elongated heart tube. (B) had mutant embryos
lacking the Na pump show impaired heart tube elongation. (C)
Heart tube elongation defects in had mutant embryos that were
injected with a mutant mRNA that encodes a Na pump lacking an
important regulatory residue (Serine 25).
the osmotic balance produced by the Na pump contributes
to the maintenance of apical junction belts, a function that
is uncovered upon loss of Nok.
Future directions
Research in our laboratory is currently directed towards
identifying and characterizing the direct downstream phosphorylation
targets of Heart and Soul/aPKCi in the context
of cell polarity and organ morphogenesis. Furthermore, we
are interested in the morphogenetic events that drive cardiogenesis.
We would like to describe the repertoire of cellular
behaviors that underlie cardiac tube elongation and
myocardial differentiation. Currently, we are generating the
tools necessary to visualize in vivo the development of the
zebrafish myocardial and endocardial tissues. In our analysis,
we will initially focus on those genes that are involved
in directed migratory behavior, control of planar or apicalbasal
cell polarity, tissue adhesion and cellular remodeling.
The identification of the molecular pathways involved in
vertebrate epithelial morphogenesis may lead to relevant
animal models for human epithelial pathologies and to the
development of novel therapeutic approaches.
Selected Publications
Rohr, S, Otten, C, Abdelilah-Seyfried, S. (2007). Asymmetric
involution from the right side of the myocardial field and directional
cohort migration generates the heart tube in zebrafish,
Circ. Res. (in press).
Bit-Avragim, N, Rohr, S, Rudolph, F, van der Ven, P, Fürst, D,
Eichhorst, J, Wiesner, B and Abdelilah-Seyfried, S. (2007).
Nuclear localization of the zebrafish tight junction protein nagie
oko. Dev. Dyn. (in press).
Cibrian-Uhalte, E, Langenbacher, A, Shu, X, Chen, JN,
Abdelilah-Seyfried, S. (2007). Involvement of Na,K ATPase in
myocardial cell junction maintenance. J. Cell Biol. 176,
223-230.
Anzenberger, U, Bit-Avragim, N, Rohr, S, Dehmel, B, Willnow, T,
Abdelilah-Seyfried, S. (2006). Elucidation of Megalin/LRP2-
dependent endocytic transport processes in the larval zebrafish
pronephros. J. Cell Sci. 119, 2127-2137.
Rohr, S, Bit-Avragim, N, Abdelilah-Seyfried, S. (2006). Heart
and soul/PRKCi and Nagie oko/Mpp5 regulate myocardial
coherence and remodeling during cardiac morphogenesis.
Development 133, 107-115.
42 Cardiovascular and Metabolic Disease Research