LABORATORY OF MOLECULAR GENETICS
Igor B. Dawid, PhD, Chief

Led by Tom Sargent, the Section on Vertebrate Development has shown that the transcription factor AP-2 is critically required for the formation of both the epidermis and the neural crest in the frog Xenopus laevis.
 

Also working with Xenopus, Igor Dawid and colleagues in the Section on Developmental Biology have shown that cell movements in gastrulation that generate the embryonic axis are regulated by the transcription factor Xlim1 through its activation of the cell adhesion molecule Paraxial Protocadherin. The group has further isolated a novel feedback inhibitor of the fibroblast growth factor pathway, named Sef.
 

Brant Weinstein and his colleagues in the Unit on Vertebrate Organogenesis have made considerable progress in their study of the formation of the vascular system in the zebrafish. Using transgenic fish in which endothelial cells express green fluorescent protein (GFP), the group was able to follow cellular detail of vessel formation in the live embryo. Further, the investigators showed that phospholipase C-gamma1 is a critical factor regulating vessel formation.
 

Also working with zebrafish, Ajay Chitnis, who heads the Unit on Vertebrate Neural Development, and colleagues identified the gene affected in the mindbomb mutant as encoding a novel E3 ubiquitin ligase. The enzyme modifies the Notch ligand Delta, thereby inducing its endocytosis and enhancing Delta/Notch signaling during neurogenesis. Given the wide-ranging significance of the Notch pathway, finding a novel component in this pathway represents a major advance in the field.
 
Robert Weisberg and his colleagues in the Section on Microbial Genetics studied the mechanism of antitermination in bacteriophage lambda, a process that controls gene expression at the stage of termination of transcription.

In the area of retroviruses, Judith Levin's group, the Section on Viral Gene Regulation, studied reverse transcription in the HIV life cycle. In particular, researchers focused on the role of nuclear capsid as a chaperone, showing that it acts to ensure effective viral DNA synthesis.
 

Working with bacteria, Mike Cashel, who leads the Section on Molecular Regulation, has studied the mechanism of general metabolic control that is mediated by a small molecule, guanosine tetra/ pentaphosphate. He has been investigating the synthesis and degradation of this regulatory factor.

In nucleic acid metabolism, a class of enzymes that degrade RNA when duplexed with DNA plays a significant role. For some time, Robert Crouch has studied these enzymes, named RNasesH. In the past year, he and his colleagues in the Section on Formation of RNA made the interesting observation that mouse embryos lacking one form of RNaseH are not viable because they are incapable of replicating their mitochondrial (mt) DNA. The role of RNaseH in mtDNA replication is a novel and important finding that also informs hypotheses of mtDNA replication.
 

Using the fruit y Drosophila, Judy Kassis and her colleagues in the Section on Gene Expression demonstrated the relationship between two transcriptional repressors, Pleiohomeotic and Pho-like, in the control of broad classes of genes.
 

For some time,Jim Kennison and his colleagues in the Section on Drosophila Gene Regulation have studied the large and important class of transcriptional activators named the Trithorax group; he discovered most of its members by genetic means. The past year witnessed the detailed analysis of the gene named tonalli, which interacts with other members of the group in the regulation of numerous genes.