of the Max - MDC

Cell Polarity and Epithelial
Morphogenesis
Salim
Abdelilah-Seyfried
Epithelial cells polarize along their apico-basal and planar axes and separate apical from basolateral membrane
compartments during development. Mature epithelial cells are highly polarized with separate apical and basolateral
membrane compartments, each with a unique composition of lipids and proteins. Within mature epithelial
tissues, cell polarity regulates cellular morphology, intracellular signaling, asymmetric cell division, cell migration,
cellular and tissue physiology as well as complex organ morphogenesis. We are interested in the molecular mechanisms
that regulate the polarization of epithelial cells and are using zebrafish and fruitfly Drosophila as our experimental
systems. We would like to understand: How do the different protein complexes that establish cell polarity
interact with each other? What are the signals by which cell polarity is mediated within cells? How is cell polarity
regulated within epithelial sheets during morphogenesis of tissues and organs? How is cell polarity linked to the
morphogenesis of the early zebrafish heart? Several zebrafish mutants with defects of epithelial cell layers will help
us to address these issues. Our long term interest is to understand how the cellular mechanisms controlling cell
polarity shape our own bodies.
Asymmetric behaviors of myocardial cells drive
zebrafish heart tube formation
Many vertebrate organs are derived from monolayered
epithelia that undergo morphogenesis to acquire their
shape. Little is known about the tissue movements and cellular
changes underlying early cardiac morphogenesis.
Heart development in zebrafish involves the fusion of two
myocardial progenitor fields at the embryonic midline.
These heart fields derive from the left and right lateral plate
mesoderm. Fusion of the two heart fields forms the heart
cone, a central flat disc which is subsequently transformed
into the primary heart tube. Morphogenetic processes and
tissue dynamics required for heart cone-to-tube transition
are not well understood (Figure 1).
We have now described the transition of the flat heart field
into the primary linear heart tube in zebrafish. Asymmetric
involution of the myocardial epithelium from the right side
of the heart field initiates a complex tissue inversion which
creates the ventral floor and medial side of the primary
heart tube. Myocardial cells that are derived from the left
side of the heart field contribute exclusively to the dorsal
roof and lateral side of the heart tube. heart and soul/aPKCi
mutants which are characterized by disrupted epithelial
organization of the myocardium fail to form an involution
fold and subsequently a heart tube. During heart tube formation,
asymmetric left-right gene expression of lefty2
within the myocardium correlates with asymmetric tissue
morphogenesis. Time-lapse analysis combined with genetic
and drug inhibition experiments revealed that motility of
the myocardial epithelium is a Myosin II-dependent migration
process. Therefore, our results demonstrate that asymmetric
morphogenetic movements of the two bilateral
myocardial cell populations generate different dorsoventral
regions of the zebrafish heart tube.
Na + ,K + ATPase interacts with Nagie oko in
maintaining myocardial polarity
In another study, we demonstrated the importance of correct
ion balance for junctional maintenance and epithelial
character of epithelial cells. Na + ,K + ATPase, or Na pump, is
an essential ion pump involved in regulating ionic concentrations
within epithelial cells. We investigated the developmental
function and regulatory mechanisms of this ion
pump. The zebrafish α1B1 subunit of Na + ,K + ATPase is
encoded by the heart and mind (had) locus and had mutants
show delayed heart tube elongation (Figure 2). This phenotype
is reminiscent of the heart and soul/aPKCi and nagie
oko (nok) mutant phenotypes which are characterized by a
lack of epithelial cell polarity. In genetic interaction studies,
Had/Na + ,K + ATPase and Nok interacted in the maintenance
of apical myocardial junctions raising the intriguing
possibility that the ion balance produced by the Na pump is
critical in this process. To functionally characterize the role
of the ion pump function, we produced a mutant form of
Had/Na + ,K + ATPase which specifically affects the ATPase
activity that is essential for pumping sodium across the
plasma membrane and found that it could not rescue the
heart tube elongation phenotype. Our study suggests that
Cardiovascular and Metabolic Disease Research 41