Integrated computational and experimental study of embryonic patterning by sequential and oscillatory gene regulatory mechanisms

• Applicant: Professor Dr. Martin Klingler, since 9/2022
• Subject Area: Developmental Biology ; Bioinformatics and Theoretical Biology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 418594528

• Final Report Year: 2024

Final Report Abstract

Animals begin life as a single cell, the zygote, which divides and specializes to form a complex multicellular organism. This remarkable process involves cells dividing and differentiating in both space and time during embryonic development. This differentiation, known as embryonic patterning, is driven by differential gene expression. Recent findings suggest that in many developing tissues across various organisms, embryonic patterning is initially a temporal process that later translates into spatial organization. Rhythmic and sequential gene activities play a crucial role in this spatial patterning. For example, a molecular clock controls gene expression stripes that define vertebrate somites, segments in short-germ arthropods, and lateral roots in plants. Sequential, non-periodic gene activation is involved in the spatial patterning of Drosophila neuroblasts, the vertebrate neural tube, and anterior-posterior fate map specification in insects. In this project, we investigated the anterior-posterior patterning of the flour beetle, Tribolium castaneum, to study how sequential and oscillatory gene activities are translated into spatial patterns during embryogenesis. Our findings support a model where this translation is mediated by the modulation of the speed of these gene activities. Specifically, the data align with a model where a balance is set between two genetic modules: one inducing dynamic changes in gene expression and another stabilizing these changes. The results of this project offer new insights into embryonic pattern formation, potentially leading also to advancements in health-related research and biotechnology.

Publications

• A systems-level view of pattern formation mechanisms in development. Developmental Biology, 460(1), 1.
  Müller, Patrick & El-Sherif, Ezzat
  
• Geometric models for robust encoding of dynamical information into embryonic patterns. eLife, 9.
  Jutras-Dubé, Laurent; El-Sherif, Ezzat & François, Paul
  
• Speeding up anterior-posterior patterning of insects by differential initialization of the gap gene cascade. Developmental Biology, 460(1), 20-31.
  Rudolf, Heike; Zellner, Christine & El-Sherif, Ezzat
  
• Patterning with clocks and genetic cascades: Segmentation and regionalization of vertebrate versus insect body plans. PLOS Genetics, 17(10), e1009812.
  Diaz-Cuadros, Margarete; Pourquié, Olivier & El-Sherif, Ezzat
  
• How enhancers regulate wavelike gene expression patterns. eLife, 12.
  Mau, Christine; Rudolf, Heike; Strobl, Frederic; Schmid, Benjamin; Regensburger, Timo; Palmisano, Ralf; Stelzer, Ernst HK; Taher, Leila & El-Sherif, Ezzat