Science...It works, Bitches!

It's time to finally put aside the car religious fish symbols and the darwinian fish with feet.  Recent work is elucidating one of the crucial juicy mysteries in evolutionary biology: how did fins become limbs?


Published online at Nature, a team of researchers describe 2 proteins essential to fin development in bony fishes and the loss of which may have been a key step in the evolution of tetrapods (4-legged vertebrates).  During a routine screen for genes involved in fin regeneration in the zebrafish labs of Marie-Andree Akimenko and Marc Ekker at the University of Ottawa in Canada, the team noted a remarkable pattern among two of many unknown genes revealed by the screen: a unique and specific localization along the early median fin fold, which runs along a fish's back, and in the pectoral fin buds, fins that grow on each side of the fish's body behind the gills.  This gene expression pattern suggests the proteins are structural components of actinotrichia, the thin, rigid fibrils that form the scaffold of developing bony fins.  The team named the proteins actinodin 1 and 2 (And1, And2) and noted that along with related genes from a database, and3 and and4, were entirely absent in tetrapods.


Using morpholinos (molecules that transiently silence gene expression) to knock down these genes, and1 and and2, the team discovered that the genes are partly redundant, but necessary for fin formation.  If only one of the genes was knocked down, fin development was normal.  However, if both genes were knocked down, actinotrichia didn't form and thus there was no regional recruitment of mesenchymal cells (fin bone precursors).  Other gene expression patterns important for fin patterning in the region were also extensively disrupted during the double knockdown, including those for fibroblast growth factor and sonic hedgehog.  Interestingly, the knockdown gene expression profile in the zebrafish, is highly similar to experimental chick and mouse mutants called Gli3, which results in polydactyly (the presence of numerous extra digits).  Even more noteworthy, one of the earliest aquatic tetrapods, Acanthostega, had 8 digits on each hand, which may indicate that loss of actinotrichia in ancestral tetrapods may have been conducive to limbs resembling polydactyly.


Their conclusion: "The loss of formation of actinotrichia during evolution may have induced profound changes in the morphology of the adult pectoral fins that perhaps led to short appendages without lepidotrichia and to gene expression profiles conducive to polydactyly in the earliest tetrapod species. Thus, the loss of actinotrichia may have contributed to the evolutionary transition from fin to limb."


The team's next steps are to use alternative methods of gene silencing of and1 and and2 (remember that morpholinos are only transient silencers) to see whether the fin ray will develop and what it will look like (perhaps a limb with multiple digits?!).  The team may also introduce the gene into tetrapod species and see if they can cause fins in normally limbed animals.