During embryonic development each body part is programmed to contain an accurate number and arrangement of cells. This accuracy is achieved through precise regulation of cell proliferation in the face of the molecular noise characteristic of the biochemical processes regulating the cell cycle. The molecular mechanisms by which embryos suppress noise remain poorly understood. Uncovering these mechanisms is a central goal of Developmental Biology and requires the development of novel methodologies to measure quantitatively cellular dynamics in living embryos. The overarching goal of this proposal is to reveal the molecular mechanisms that ensure accurate control of the cell cycle during Drosophila embryonic development. We will study the molecular mechanisms ensuring precise temporal regulation of cell division through control of gene expression, signaling and protein degradation. We have developed live imaging and computational approaches to quantify the dynamics of the major enzymes regulating the cell cycle during embryonic development.
In Aim 1, we will use biosensors for the activities of of Cdk1 and Chk1 to identify how chemical waves act to synchronize mitosis in the syncytial embryo.
In Aim 2, we will use live imaging to dissect the molecular mechanisms that ensure the cell cycle remodeling at the maternal-to-zygotic transition.
In Aim 3, we will elucidate how transcriptional regulation of cdc25string ensures precise regulation of the timing of mitosis during gastrulation. These experiments will define a novel quantitative framework for uncovering how the cell cycle is regulated accurately during embryonic development.
Our project addresses the fundamental question of how the cell division cycle is timed precisely during embryonic development. Such precision is required for normal development and function of multicellular tissues. Perturbations of the timing of the cell cycle can lead to embryonic lethality and diseases, including cancer.
| Vergassola, Massimo; Deneke, Victoria E; Di Talia, Stefano (2018) Mitotic waves in the early embryogenesis of Drosophila: Bistability traded for speed. Proc Natl Acad Sci U S A 115:E2165-E2174 |
| Deneke, Victoria E; Di Talia, Stefano (2018) Chemical waves in cell and developmental biology. J Cell Biol 217:1193-1204 |
