Becker Lab

We use the zebrafish as a model for the evolution of vertebrate genomes and for genomics of human disease. For example, all vertebrates have a very similar complement of genes, yet come in very different shapes and sizes. How do vertebrate genomes achieve these differences using essentially the same genes? The answer, in large part, is that the regulation of key developmental genes differs in different vertebrates (these are genes with regulatory function that have been characterized through their roles in animal development through genetic screens in model organisms such as fruit flies, zebrafish and mice). Differences in gene regulation, in evolution, have been achieved by exposing these genes to new regulatory sequences that may have had other roles previously, for example as mobile DNA elements or viruses, or may have originated from other regions of the same genome. While the precise regulation of this select group of genes is necessary to build a vertebrate organism, subtle mis-regulation of these genes may result in human disease. For example, type 2 diabetes may result when insufficient numbers of insulin-producing cells are made, or when these cells produce insufficient quantities of insulin, processes that are regulated by developmental genes. Likewise, subtle alterations in the generation of neuronal numbers or –connections within the human brain may result in psychiatric disease. Our group has shown that genomic regions involved in the regulation of developmental genes are large, evolutionary conserved segments of chromosomes and often stretch over multiple genes. We now aim to resolve human diseases that have been mapped to these regions by testing human regulatory DNA in transgenic zebrafish to pinpoint which genes are involved in human neurological diseases, and how mis-regulation of these genes may result in the observed defects. The current focus of the group is on characterizing gene regulation in the vertebrate brain of chromosomal loci implicated in obesity, and several types of psychiatric disorders.