Office: (613) 562-5800 ext. 7399
Work E-mail: makimen@uOttawa.ca
The research focus in my lab is on the characterization of the molecular mechanisms underlying fin development and regeneration. Contrarily 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 that 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 almost 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. Current studies are focused on the control of pattern formation of the fin rays during fin regeneration. In parallel to these studies, we performed a screen for genes differentially expressed during fin regeneration. This screen 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. For example, this screen allowed us to identify a new gene family that is coding for components of the actinotrichia, fish fin-specific fibrils. This gene family that we called actinodin (and) is only found in fish and has been lost from the genomes of tetrapod species during evolution. Functional analysis of these genes suggests that loss of actinotrichia during evolution may have also caused the loss of fin rays, an important step in the transformation of fins into limbs. Furthermore, gene expression profile in fish missing the actinotrichia may offer a potential reason why ancestral tetrapods had multiple digits. We are further characterizing the function and evolution of this gene family and the regulation of its expression.
- Zhang, J., Wagh, P., Guay, D., Sanchez-Pulido, L., Korzh, V., Andrade, M., Akimenko, M.-A. Loss of actinotrichia and the fin-to-limb transition. Nature 466, 234-237, 2010
- Smith, A., Zhang, J., Guay, D., Quint, E., Johnson, A., Akimenko, M.-A. Gene expression analysis on sections of zebrafish regenerating fins reveal limitations in the whole-mount im situ hybridization method. Developmental Dynamics 237, 417-425, 2008
- Rolland-Lagan, A.-G., Paquette, M., Tweedle, V. and Akimenko, M.-A. Morphogen-based simulation model of ray growth and joint patterning during fin development and regeneration. Development (2012) 139, 1188-1197, 2012
- Zhang, J., Jeradi, S., Strähle, U. and Akimenko, M.-A. Laser ablation of the sonic hedgehog-expressing cells during fin regeneration affects ray branching morphogenesis. Developmental Biology (2012) 365, 424-433, 2012
- McMillan, S.C., Xu, T., Zhang, J., Teh, C., Korzh, V., Trudeau, V.L. & Akimenko, M.-A. Regeneration of breeding tubercles on the pectoral fins of zebrafish requires androgens and two waves of re-vascularization. Development (2013) 140, 4323-4334, 2013