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.
 
Representative papers:
 
Cohn, M.J. and Tickle, C. (1999) Developmental basis of limblessness and axial regionalization in snakes. Nature. 399: 474-479.
 
Cohn, M.J. (2002).Lamprey Hox genes and the origin of jaws. Nature. 416:386-387.
 
Freitas, R. and Cohn M.J. (2004). Analysis of EphA4 in the lesser spotted catshark identifies a primitive gnathostome expression pattern and reveals co-option during evolution of shark-specific morphology. Development, Genes and Evolution. 214:422-428.
 
Molecular Genetics of External Genital Development
 
 

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.
 
Representative papers:
 

Petiot, A., Perriton, C.L., Dickson, C., and Cohn, M.J. (2005). Development of the mammalian urethra is controlled by Fgfr2-IIIb. Development. 132 (10): 2441-2450

Cohn, M.J. (2004). Developmental genetics of the external genitalia. Advances in Experimental Medicine and Biology. 545: 149-57.

Perriton, C. L., Powles, N., Chiang, C., Maconochie, M., and Cohn, M. J. (2002) Sonic hedgehog signaling from the urethral plate controls external genital development. Developmental Biology. 247:26-46.