FORMINS - PROTEINS DEDUCED FROM THE ALTERNATIVE TRANSCRIPTS OF THE LIMB DEFORMITY GENE

VERTEBRATE limb formation is an evolutionarily conserved process programmed by an array of morphogenetic genes1-5. As a result of transgene insertion, we previously identified a mutation at the mouse limb deformity (Id) locus that disrupts embryonic pattern formation, resulting in a reduction and fusion of the distal bones and digits of all limbs as well as variable incidence of renal aplasia2,6-9. We have now characterized the Id locus at the molecular level. It contains evolutionarily conserved coding sequences that are transcribed in adult and embryonic tissues as a complex group of low abundance messenger RNAs created by alternative splicing and differential polyadenylation. The association of these transcripts with the gene responsible for the mutant phenotype was established by demonstrating that they are disrupted in two independently arising Id alleles8. We have now deduced the structure of several novel proteins (termed formins) from the long open reading frames encoded by the various Id transcripts. The observation of these different RNA transcripts in different tissues suggests that the formins play a part in the formation of several organ systems. © 1990 Nature Publishing Group.