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  1. Abstract

    Regulation of the homeodomain transcription factor WUSCHEL concentration is critical for stem cell homeostasis inArabidopsisshoot apical meristems. WUSCHEL regulates the transcription ofCLAVATA3through a concentration-dependent activation-repression switch.CLAVATA3, a secreted peptide, activates receptor kinase signaling to repressWUSCHELtranscription. Considering the revised regulation,CLAVATA3mediated repression ofWUSCHELtranscription alone will lead to an unstable system. Here we show thatCLAVATA3signaling regulates nuclear-cytoplasmic partitioning ofWUSCHELto control nuclear levels and its diffusion into adjacent cells. Our work also reveals that WUSCHEL directly interacts with EXPORTINS via EAR-like domain which is also required for destabilizing WUSCHEL in the cytoplasm. We develop a combined experimental and computational modeling approach that integratesCLAVATA3-mediated transcriptional repression ofWUSCHELand post-translational control of nuclear levels with the WUSCHEL concentration-dependent regulation ofCLAVATA3. We show that the dual control by the same signal forms a seamless connection between de novo WUSCHEL synthesis and sub-cellular partitioning in providing robustness to the WUSCHEL gradient.

     
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  2. Abstract The exact mechanism controlling cell growth remains a grand challenge in developmental biology and regenerative medicine. The Drosophila wing disc tissue serves as an ideal biological model to study mechanisms involved in growth regulation. Most existing computational models for studying tissue growth focus specifically on either chemical signals or mechanical forces. Here we developed a multiscale chemical-mechanical model to investigate the growth regulation mechanism based on the dynamics of a morphogen gradient. By comparing the spatial distribution of dividing cells and the overall tissue shape obtained in model simulations with experimental data of the wing disc, it is shown that the size of the domain of the Dpp morphogen is critical in determining tissue size and shape. A larger tissue size with a faster growth rate and more symmetric shape can be achieved if the Dpp gradient spreads in a larger domain. Together with Dpp absorbance at the peripheral zone, the feedback regulation that downregulates Dpp receptors on the cell membrane allows for further spreading of the morphogen away from its source region, resulting in prolonged tissue growth at a more spatially homogeneous growth rate. 
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  3. null (Ed.)
  4. Maini, Philip K. (Ed.)