Previous and Current Research

Regeneration is a process that completely re-grows lost structures from a tissue stump.  The zebrafish has a very extensive ability to regenerate lost compound structures such as appendages and organs, and the goal of my research is to understand how the zebrafish activates and regulates molecular programs that allow it to regenerate these structures.

Forward genetic approach to identify and characterize genes required for regeneration.
To accomplish this goal, my group has performed screens for mutant adult and larval fish that fail to regenerate the caudal fin properly.  From these screens, I have several larval and adult mutants that display either no regeneration, partial regeneration or mispatterned regeneration.  My group is currently characterizing the cellular and molecular biology associated with these mutations and mapping (locating) the mutations in the genome to find the genes responsible for the mutant phenotypes. 

Reverse genetic approach to identify and characterize genes involved in regeneration.
In addition to using mutagenesis screens, I have undertaken microarray profiling to identify genes that are active during the regeneration of the fin appendage and the heart.  The microarrays are yielding data that are contributing to candidate-based discoveries.  fam53b and mdka are two molecules that we identified and are currently characterizing.

Characterizing the role of fam53b in cell proliferation and gene transcription during zebrafish appendage regeneration.
Two hallmarks of epimorphic regeneration are extensive cell proliferation and the reactivation of genes involved in embryonic development.  The gene fam53b (family with sequence similarity 53-member b) is expressed in regenerating tissue that is highly proliferative.  Furthermore, when we knockdown of fam53b in regenerating caudal fins, we observe reduced regenerative outgrowth and a significant reduction of proliferating cells, suggesting that fam53b controls a pro-regeneration cell proliferation program.  In addition to the involvement of fam53b in cell proliferation, we observe that the presence of this gene is also involved in the regulation of specific pro-regeneration genes, namely, msxb and sonic hedgehog, two genes required for appendage regeneration.  My group is currently investigating the biological role that fam53b has in controlling cell proliferation and in regulating gene transcription in regenerating structures.

Characterizing the role of midkine signaling in heart and appendage regeneration.
In addition to fam53b, my group is researching the role of another gene in the regeneration process.  The gene midkine-related growth factor a (mdka) is highly expressed early during the regeneration process both in the fish heart and fin appendage, and its expression remains on as structural regeneration proceeds.  Knock down of mdka results in a reduction in the regenerative outgrowth of the fin, indicating that it has an important role in the regulation of formation of new tissue.  Because mdka is a extracellular ligand, we are working to identify the appropriate transmembrane receptors.

Future Goals and Projects

The fundamental goal of regenerative medicine is to replace damaged or lost tissues with healthy tissues.  The identification of the genes—and their molecular mechanisms—involved in epigenetic regeneration can offer pharmaceutical targets for therapies designed to restore function to damaged organs and appendages. 

My goal is to get the genes involved in the initiation and maintenance of pro-regeneration signals and to use these genes to understand the cellular and molecular biology of the epimorphic regeneration. 

• Characterization of acquired regeneration mutants and identify the genes causing the phenotype.

• Identify the molecular mechanism(s) regulating fam53b and its control on cell proliferation and gene transcription.

• Characterize the molecular mechanism(s) of midkine-related growth factor in heart and fin regeneration.

• Further screens for molecules required for epimorphic regeneration.

Group Members

List of group members

Selected Publications

Rojas-Munoz A, Rajadhyksha S, Gilmour D, van Bebber F, Antos C, Rodriguez Esteban C, Nüsslein-Volhard C, Izpisua Belmonte JC., ErbB2 and ErbB3 regulate amputation-induced proliferation and migration during vertebrate regeneration. (2009) Dev. Biol. 327: 177-190.

Kizil C, Otto GW, Geisler R, Nüsslein-Volhard C, Antos CL. Simplet controls cell proliferation and gene transcription during zebrafish caudal fin regeneration. Dev Biol. (2009) Vol. 325: 329-340.

Luckey SW, Mansoori J, Fair K, Antos CL, Olson E, Leinwand LA., Blocking cardiac growth in hypertrophic cardiomyopathy induces cardiac dysfunction and decreased survival only in males. (2007) American Journal of Physiology Heart Circulation Physiology  292: H838-H845.

Antos CL (Co-first authorship), Lopez-Rodriguez C, Shelton JM, Richardson JA, Lin F, Novobrantseva TI, Bronson RT, Igarashi P, Rao A, and Olson EN., Loss of NFAT5 results in renal atrophy and lack of tonicity-responsive gene expression (2004) Proceedings of the National Academy of Sciences U.S.A. 101: 2392-2397.

Antos CL, McKinsey TA, Dreitz M, Hollingsworth LM, Zhang CL, Schreiber K, Rindt H, and Olson EN., Blockade to Cardiomyocyte Hypertrophy by Histone Deacetylase Inhibitors (2003) Journal of Biological Chemistry 278: 28930-28937.

Zhang CL, McKinsey TA, Chang S, Antos CL, Hill JA, and Olson EN., Class II Histone Deacetylases Act as Signal-responsive Repressors of Cardiac Hypertrophy. (2002) Cell 110: 479-488.

Antos CL, McKinsey TA, Frey N, Kutschke W, McAnally J, Shelton JM, Richardson JA, Hill JA, and Olson EN., Activated Glycogen Synthase [Kinase]-3b Suppresses Cardiac Hypertrophy in vivo. (2002) Proceedings of the National Academy of Sciences U.S.A.99: 907-912.

Antos CL, Frey N, Marx SO, Reiken S, Gaburjakova M, Richardson JA, Marks AR, and Olson EN., Dilated Cardiomyopathy and Sudden Death Resulting from Constitutive Activation of Protein Kinase A. (2001) Circulation Research 89: 997-1004.