We are interested in how cell transformation are controlled in time during early embryogenesis and tissue regeneration. We believe that understanding timing in biology requires the integration of chemical and physical (mechanical) signals. We are busy investigating these mechanisms in Drosophila embryogenesis and zebrafish bone regeneration
Synchronization of mitosis during early Drosophila embryonic development
Collective behaviors have been observed in a variety of biological contexts, ranging from quorum sensing in bacteria to swarming in flocks of birds. However, the molecular mechanisms that control collective cell behaviors in the development of complex tissues remain largely uncharacterized. We use the Drosophila embryo as a model to identify these mechanisms during embryonic development. We are investigating the regulation of the timing of mitosis in the early syncytial embryo. We are studying how Cdk1 waves and the integration of cell cycle and mechanical signals ensure the synchronization of the cleavage cycles.
Developmental control of the cell cycle
In most metazoans, early embryonic development is characterized by rapid cleavage divisions, which are followed by the morphogenetic process of gastrulation. During these stages, the cell cycle must be precisely and rapidly reprogrammed to ensure that the process of cell division is compatible with co-occurring differentiation and morphogenesis. We have developed novel molecular markers and imaging methods to study cell cycle control during early Drosophila development and are using and expanding this quantitative methodology to dissect the molecular mechanisms ensuring the precise temporal control of cell division in response to developmental inputs. The Drosophila embryo develops as a syncytium, in which nuclei invariably undergo 13 rapid divisions prior to a pause in the cell cycle coinciding with activation of zygotic gene expression and degradation of maternal product at the maternal-to-zygotic transition (MZT). The number of divisions preceding the MZT is regulated by the ratio of DNA and cytoplasmic contents (N/C ratio) by a poorly understood mechanism. Following the MZT, morphogenesis begins and cells divide again in a highly stereotypical pattern (controlled by transcription of a single rate limiting activator: cdc25string), which exemplifies the extraordinary spatiotemporal precision by which cell divisions are controlled during embryonic development. We are studying these processes by addressing the following questions: what ensures that the correct fixed number of cell divisions precedes the maternal-to-zygotic transition (MZT)? How do embryos measure the N/C ratio? How does sensing of the N/C ratio signal to the cell cycle machinery? How is cdc25string transcription controlled to ensure the correct spatiotemporal pattern of cell divisions? Are there general strategies to obtain precise temporal control of gene expression during embryonic development? Are there post-transcriptional feedback mechanisms delaying or accelerating mitosis in response to morphogenetic clues? We believe that these experiments will reveal important principles of the control mechanisms regulating development.
Quantitative analyses of appendage regeneration in zebrafish
Zebrafish have an incredible ability to regenerate lost appendages. For example, an amputated fin is able to regenerate to its exact size and shape. At the heart of this amazing feat is the ability of zebrafish tissues to properly coordinate cell proliferation and cell differentiation during regeneration. While several mechanisms and pathways involved in the regulation of cell proliferation during appendage regeneration have been elucidated, we lack a quantitative understanding of the molecular mechanisms controlling this process. In collaboration with Dr. Ken Poss in our Department we are developing imaging methods and transgenic lines to study the dynamics of regeneration with single cell resolution.