Marie-Andrée Akimenko, PhD makimenko@ohri.ca Roger Guindon Hall (see Contact page for maps)

Affiliate Investigator, Chronic Disease, Ottawa Hospital Research Institute

Associate Professor, Department of Medicine, University of Ottawa, Canada.

Cross-Appointment, University of Ottawa, Department of Cellular and Molecular Medicine

Research Interests

My research program is focused on the characterization of the molecular mechanisms underlying fin development and regeneration.      

In contrast to mammals, adult teleost fish and some urodele amphibians have the ability to regenerate their appendages. Regeneration depends on the formation of a blastema, a group of proliferative and undifferentiated cells which will progressively differentiate as the regenerate is growing.  A set of communication mechanisms takes place between the cells that will make the regenerated part of the fin. Teleost fin regeneration is fast, fin structure is relatively simple at the cellular level, and each fin ray behaves as an independent regeneration unit, facilitating internally controlled experiments. These characteristics make it an attractive model to determine how signaling molecules control tissue patterning and growth, and how multiple pathways are coordinated.     

Our studies have been focused on the functional analysis of the hedgehog and bone morphogenetic signaling pathways during fin regeneration.   We have shown that the hedgehog signaling pathway is involved in both growth of the fin regenerate and formation and patterning of the dermal bones composing the fin rays.  We also showed that bmp signaling is both required for the growth of the regenerate and for the differentiation of the bone-secreting cells.  This study and other studies also unraveled the surprising finding that fin rays described as dermal bones are expressing factors uniquely found in the cartilage leading to the formation of endochondral bone.  These results position ray bone in an intermediate category between dermal and endochondral bones.  

In parallel to these studies, we performed a screen for genes differentially expressed during fin regeneration using suppression subtraction hybridization and DDRT-PCR. These screens yielded 322 distinct genes.  The information gathered from this study is providing resources for further investigations into the molecular mechanisms of fin development and regeneration.   We are presently performing the functional analysis of two novel genes specifically expressed in the developing and regenerating fins.     One of the major advantage of the zebrafish as a model for developmental studies is that it is amenable to genetic analysis.  The paired fins are phylogenetically related to the limbs of higher vertebrate species. Our work and that of others demonstrated that many of the genes and developmental pathways involved in fin and limb development are comparable. We are characterizing mutations affecting embryonic fin development in zebrafish obtained from the large-scale chemical mutagenesis screen performed by Driever et al. (Development (1996) 123:37-46). The availability of such models will lead to significant advance in our understanding of the basis of birth defects.

Selected publications:

Smith, A., Zhang, J., Guay, D., Quint, E., Johnson, A. & Akimenko, M.-A. Gene expression analysis on sections of zebrafish regenerating fins reveals limitations in the whole-mount in situ hybridization method. Developmental Dynamics (2008) 237, 417-425.