Title: How flies make and use their appendages
Abstract: My plan is to present an overview of the current efforts in my lab, providing necessary background when needed. I will describe our studies describing the in vitro DNA binding properties of the Hox family of transcription factors, both with and without cofactors, and then our more recent work extending our in vitro discoveries back in vivo, into the fly. The two in vivo Hox-dependent systems that I will describe are the famous transformation of the 3rd thoracic segment to a second copy of the 2nd thoracic segment (the so-called ‘bithorax’ fly) and how the pairs of legs in each thoracic segment acquire their distinct morphological identities. If there is time and interest, I will discuss our efforts to characterize the molecular identities of each of the ~50 motor neurons that innervate each leg and how these neurons connect to the rest of the neural circuitry to allow the fly to walk with all six legs in a coordinated manner.
I was first introduced to state-of-the-art biology research while an undergraduate at Cornell University where I had the fortunate opportunity to work in Gerry Fink’s lab at the time when his lab developed yeast transformation. Since then, I have been drawn to new technologies and using them to answer significant biological questions. For my Ph.D., I worked with David Baltimore at MIT, where I studied retroviruses. For my thesis I identified the sequence required in cis for packaging genomic retroviral RNA into virus particles. This discovery allowed me to construct a so-called ‘helper-free packaging cell line’ that could be used to package any RNA containing the packaging sequence into virus particles, thus marking the birth of viral vectors for gene transfer. While at MIT, I became increasingly interested in animal development. Towards the end of my Ph.D.,Rubin and Spradling developed P element technology for generating transgenicDrosophila, making this organism, together with its powerful genetics, a superb system to study development. Inspired by these tools, I moved to David Hogness’ lab at Stanford to study Hox genes in Drosophila. My choice of postdoc labs was motivated by these amazing genes, capable of transforming one body part into another, and by the pioneering molecular biology methods being used and developed in that lab. My lab still works on Hox genes, where we focus on how these transcription factors target and regulate the correct sets of down stream genes, a fundamental and still unanswered problem for most transcription factors. Our work on Hox factors led to the discovery that they often work with cofactors to achieve binding specificity. These cofactors, in turn, have profound Hox-independent functions in appendage development, which eventually led to new projects on proximo-distal axis formation in the fly leg. Most recently, our work on fly legs led to understanding how flies walk, how the motor neurons that innervate and control leg movements develop, and how locomotor circuits are assembled. These more recent projects have challenged us to learn entirely new and interesting aspects of neuroscience and development.