Congenital malformations of the external genitalia are among the most common birth defects. Approximately one in every 250 children is now born with hypospadias, a malformation affecting urethral tube development. A major focus of our lab is to understand the molecular control of external genital patterning in mammals. This project focuses heavily on the mouse as a model system, and involves molecular genetics, experimental embryology, and genomic analysis of genitourinary development. The external genitalia of males and females begin with formation of a genital tubercle. Signals that regulate early pattern formation of the genital tubercle are common to males and females, and sexual differentiation occurs relatively late in genitourinary morphogenesis. We are interested in identifying genes that (1) regulate development of the urethral tube, and (2) control outgrowth and three-dimensional patterning of the genital tubercle. We have discovered a new organizer that is essential for early outgrowth of the genital tubercle. The activity of this organizing tissue is mediated by a secreted signaling molecule called Sonic hedgehog. We have also identified a growth factor receptor that plays an essential role in urethral tube closure. This work has opened a new area of investigation, providing the opportunity to study how environmental factors influence the genetic circuitry that regulates embryonic development. The lab also has a strong interest in the evolution of external genitalia. We are addressing questions aimed at identifying the mechanisms responsible for this major morphological innovation, and understanding how genitourinary structures have diversified during tetrapod evolution.
Larkins, C. E., Enrique, A. B., and Cohn, M. J. (2016) Spatiotemporal dynamics of androgen signaling underlie sexual differentiation and congenital malformations of the urethra and vagina. Proceedings of the National Academy of Sciences USA, doi: 10.1073/pnas.1610471113.
Armfield B. A., Seifert, A. W., Zheng, Z., Merton, E. M., Rock, J. R., Lopez, M. C., Baker, H. V., and Cohn, M. J. (2016) Molecular characterization of the genital organizer: Gene expression profile of the mouse urethral plate epithelium. The Journal of Urology, May 9. pii: S0022-5347(16)30364-0. doi: 10.1016/j.juro.2016.04.091.
Zhang, Z., Armfield, B. A., and Cohn, M. J. (2015). Timing of androgen receptor disruption and estrogen exposure underlies a spectrum of congenital penile anomalies. Proceedings of the National Academy of Sciences USA 112 (52):E7194-203. doi:10.1073/pnas.1515981112
Gredler, M. L., Seifert, A. W., and Cohn, M. J. (2015) Tissue-specific roles of Fgfr2 in development of the external genitalia. Development 142, 2203-2212. doi:10.1242/dev.119891
O’Shaughnessy, K. L., Dahn, R. D., and Cohn, M. J. (2015) Molecular development of chondrichthyan claspers and the evolution of copulatory organs. Nature Communications 6:6698. DOI: 10.1038/ncomms7698
Herrera, A. M. and Cohn, M. J. (2014) Embryonic origin and compartmental organization of the external genitalia. Scientific Reports, 4 (6896):1-6. DOI: 10.1038/srep06896
Herrera, A. M., Shuster, S. G., Perriton, C. L., and Cohn, M. J. (2013) Developmental basis of phallus reduction during bird evolution. Current Biology 23:1065-74. DOI: 10.1016/j.cub.2013.04.062
Seifert, A. W., Zheng. Z, Ormerod, B. K., and Cohn, M. J. (2010). Sonic hedgehog controls growth of external genitalia by regulating cell cycle kinetics. Nature Communications 1:23, DOI:10.1038/ncomms1020.
Seifert, A. W., Bouldin, C., Choi, K. S. Harfe, B. D. and Cohn, M. J. (2009). Multiphasic and tissue-specific roles of Sonic hedgehog in cloacal septation and external genitalia development. Development. 136:3949-57.*
Seifert, A. W., Yamaguchi, T., and Cohn, M. J. (2009). Functional and phylogenetic analysis shows that Fgf8 is not required for external genital development. Development 132: 2643-51
Evolution of Vertebrate Limb Development
Our lab aims to understand the molecular genetic mechanisms responsible for the evolution of fins and limbs. How the vertebrate limb is constructed during embryonic development is becoming increasingly clear, but comparatively little is known about how this genetic program has evolved to generate the impressive morphological diversity seen across vertebrates. This project is focused on identifying the developmental genetic causes of major evolutionary changes to the vertebrate body, such as the origin of fins, the transition of fins to limbs, and loss of limbs in animals such as snakes and whales. These questions are being addressed by a comparative approach to developmental biology, in which the molecular control of embryonic development is studied in a range of organisms that sit at key phylogenetic positions.
Tarazona, O. A., Lopez, D. H., Slota, L. A, and Cohn, M. J. (2019). Evolution of limb development in cephalopod mollusks. eLife 8:e43828. doi:10.7554/eLife.43828
Leal, F. and Cohn, M. J. (2016). Loss and re-emergence of legs in snakes by modular evolution of Sonic hedgehog and Hoxd enhancers. Current Biology 26 (21): 2966-2973, doi: dx.doi.org/10.1016/j.cub.2016.09.020
Tarazona, O. A., Slota, L. A., Lopez, D. H., Zhang, G., and Cohn, M. J. (2016) The genetic program for cartilage development has deep homology within Bilateria. Nature, 533 (7601): 86-89. PMID: 27111511
O’Shaughnessy, K. L., Dahn, R. D. and Cohn, M. J. (2015) Molecular development of chondrichthyan claspers and the evolution of copulatory organs. Nature Communications 6:6698. DOI: 10.1038/ncomms7698
Zheng, Z. and Cohn, M. J. (2011) Developmental basis of sexually dimorphic digit ratios. Proceedings of the National Academy of Sciences USA 108: 16289-94.
Zhang, G. and Cohn, M. J. (2006). Hagfish and lancelet fibrillar collagens reveal that type II collagen-based cartilage evolved in stem vertebrates. Proceedings of the National Academy of Sciences USA. 103: 16829-16833.
Freitas, R. Zhang, G. and Cohn, M. J. (2006). Evidence that mechanisms of fin development evolved in the midline of early vertebrates. Nature, 442:1033-1037.
Post Doctoral Fellow: University of Reading, U.K.
Ph. D. University College London, U.K.
M.A., Kent State University
B.A., University of Texas at Austin
Awards, Professional Service:
Doctoral Dissertation Mentoring Award, University of Florida, 2018-19.
Basic Science Research Award, University of Florida College of Medicine, 2018.
Orbis Pictus Award, International Society for Transgenic Technologies and Czech Center for Pharmacogenomics, 2017.
Board of Directors, Society for Developmental Biology, 2015-2018.
Howard Hughes Medical Institute Early Career Scientist, 2009-2015.
Meredith Campbell Award, American Urological Assoc./Society for Pediatric Urology, 2013
Postdoctoral Mentoring Award, University of Florida, 2013.
Senior Faculty Research Award, Sigma Xi, UF Chapter, 2012.
BBSRC David Phillips Research Fellowship, 1998-2003.
GMS 6013 Developmental Genetics (course co-director)
GMS 6005 Fundamentals of Developmental Biology
GMS 6905 BMS Laboratory Rotations
GMS 7979 Advanced Research
GMS 7980 Doctoral Research
BMS 4905 Undergraduate Research