Sources of Diversity in Axon Patterning: Roles of the Many Isoforms of the Transcription Factor, Lola

点击翻译按钮获取中文摘要

It used to be thought that the human genome had 100,000 or even 1,000,000 genes, but now we know that the real number is closer to 30,000. And yet, this modest-sized genome has to encode the blueprint for a brain and nervous system of unimaginable complexity. How does a small number of genes specify all of this complexity?Part of the answer seems to be in how one counts the number of genes. In the fruit fly, there is a gene called "Lola" that specifies the connections between nerve cells. Recent studies have shown that this one gene comes in 20 different forms, and these studies hint that those 20 different forms may allow this single gene to do the work of 20 different genes. Moreover, those twenty forms seem to be able to pair up in different combinations, so that they can effectively act like a family of several hundred genes - yet all are encoded by "one" gene, lola. The goal of this proposal is to test in detail this idea that one gene can be made to do the work of dozens, or hundreds of genes, and to understand what implications that finding has for how a nervous system is built. The activities of several of these differing forms will be tested, by knocking out the forms, one at a time, or knocking out one and adding back a different one. The interactions among these forms will also be tested, in a similar way. What is learned about lola in fruit flies is certain also to tell us how the few genes in the human genome can work together in different combinations to specify the complexity of the human nervous system. The PI is actively involved in training of undergraduate and graduate students and this project will offer rich opportunities in research experience.