Research

Temporal Regulation

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Drosophila embryos

Embryogenesis is extremely well coordinated in time yet we have little knowledge of how embryos ensure such temporal robustness. We take three multiscale approaches to tackling this problem. (i) Embryo scale: By recording the development of hundreds of Drosophila embryos, we are developing the first quantitative analysis of the temporal robustness of a developing organism. (ii) Tissue scale: Cell fate specifcation must be highly temporally regulated. We use the zebrafish myotome – which has numerous different cell types specified during a relatively short period – to study when cell fate is specified. (iii) Subcellular scale: The precise readout of genes is essential for high temporal coordination. We use FCS and optogenetic approaches to in vivo measure transcription factor kinetics (especially binding) and hence develop one of the first truly spatio-temporal maps of gene regulation.


Cell Migration

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Patterning in the early
Drosophila embryo

Recent work in Drosophila and vertebrate systems has highlighted the important role that cell migration plays in organogenesis. To gain insight into how cell migration is regulated to ensure precise final patterning we use both Drosophila and zebrafish embryogenesis. (i) In the zebrafish myotome, cells migrate significant distances after migration. We explore how these cells remain coordianted during complex 3D tissue morphogenesis. (ii) During Drosophila embryogenesis, the central nervous system extends along almost the entire embryo anterior-poster axis before then retracting to its final size. This process involves significant biomechanical shifts in the CNS and also cell death. We use AFM, live imaging and an extensive library of CNS mutants to develop a mechanical map of the CNS formation. (iii) Despite disrupting initial patterning, many patterning genes do not result in lethal phenotypes. We are exploring using lightsheet microscopy when and how patterning defects are repaired during development.


Scaling

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Gut scaling in Drosophila
embryo

Organs are the central component of a functioning organism, yet how organs form, grow and scale precisely is largely unknown. (i) We use formation of the Drosophila embryo heart - which is comprised of a fixed number of cells (104) - to examine how cells reliably find their counterparts, how errors are corrected, and how an organ of fixed cell number interacts and scales with nieghboring tissues and organs. (ii) We use formation of the embryonic Drosophila gut to explore how complex shapes form, and in particular, how these shapes scale to embryo size.


Gap gene expression patterns in cycle 14 Drosophila embryo

 


Robustness analysis of the temporal readout of a morphogen gradient [14]

 


Anterior of Drosophila embryo during cellularization expressing nucleus (red) and membrane (green) markers