Regulation of temporal patterning in neural progenitors and subsequent generation of neural diversity

Generation of neural diversity is a key question in developmental neurobiology. Studies in both vertebrates and Drosophila have shown that neural progenitors are temporally patterned to generate different neural types in a defined order. We use the Drosophila medulla (the first color-information processing center) to address this question. Through an antibody screen, we identified a large set of transcription factors expressed in the developing medulla, and five of them, Homothorax (Hth), Eyeless (Ey), Sloppy paired 1 and 2 (Slp), Dichaete (D) and Tailless (Tll), are expressed sequentially in neural progenitors called neuroblasts as they age. These temporally-expressed transcription factors are required for sequential generation of different neural types. Cross-regulation between these transcription factors is required but not sufficient for temporal transitions, suggesting additional mechanism is required.

My lab’s goal is to elucidate the molecular mechanism controlling the sequential temporal transitions in medulla neuroblasts to generate different neural types, using both genetics and genomics approaches. In a genomics approach, we compare the transcriptome profiles of medulla neuroblasts as they transit through different temporal stages using the five transcription factors as markers. In parallel, we use genetic analysis to identify the molecular players and elucidate the molecular clock. The integrated approaches are also used in our investigation of how the sequential expression of transcription factors in neuroblasts generates neural diversity. Our research will shed light on the neurogenesis of a complex adult neural structure, as well as on the general mechanism of temporal patterning of neural progenitors.