Feng Liu
Princeton University
Title : Testing threshold-dependent model for cell fate controlling during Drosophila embryogenesis
Abstract :

Understanding the cell fate controlling in cellular programing and reprograming is a key to tissue engineer and regenerative medicine. We choose Drosophila embryos as our model system to unravel the underling mechanism for cellular programming during embryogenesis. As predicted by the threshold-dependent model, cell fate determination is executed by genetic networks that respond to absolute concentrations of transcription factors. To test this model, we manipulated the absolute concentration of the maternally supplied transcription factor Bicoid and measure the cell fate map shift in response to the Bicoid concentration perturbation. When we increase the overall amount of Bicoid 5-fold, Bicoid concentrations in cells at positions of the cephalic furrow, an early morphological marker, differ by a factor of two. This finding apparently contradicts the traditional threshold-dependent readout model, which predicts that the Bicoid concentrations at these positions should be identical. In contrast, Bicoid concentration at target gene expression boundaries is nearly unchanged during early developmental times, but adjusts dynamically toward the same 2-fold change as development progresses. Thus the cell fate map responds faithfully to Bicoid concentration during early development, in agreement with the threshold model, but subsequently partially adapts in response to altered Bicoid dosage, driving segmentation patterns towards their wild-type positions. This dynamic response requires other maternal regulators such as Torso and Nanos, suggesting that cell fate determination is established by the integration of multiple maternal inputs.

Biography :

Dr. Feng Liu is a Research Scientist in the Physics Department of Princeton University. He received his Ph.D. in Biophysics and Computational Biology from University of Illinois at Urbana and Champaign, MS in Nuclear Engineer from Beijing University, and BS in physics from Shandong University. His expertise lies in biophotonics, quantitative imaging process, and computational biology. His Ph.D. work was focused on protein folding, protein aggregation, protein engineering, spectroscopy, and molecular dynamics simulations. The proteins designed by him could fold with extremely fast speed (reaching the folding limit) and were served as benchmark proteins for molecular dynamics simulations. One of his papers in reporting such fast folding process was selected as the “2009 highlighted article” by the editor of Journal of Chemical Physics. His paper reporting the force field bias in the molecular dynamics simulation has been cited almost 200 times since its publication in 2008. Currently he focuses on the cell program during Dorsophila embryogenesis fly embryos using quantitative two-photon microscopy, genetics and mathematical modeling. His work on quantitatively testing threshold model in cell fate determination was recently published in PNAS and highlighted by Nature Reviews Genetics. As a young investigator, Dr. Feng Liu has published a series of papers in prestigious journals such as PNAS, JMB, and Biophysical Journal.


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