TY - JOUR TI - Strength of interactions in the Notch gene regulatory network determines patterning and fate in the notochord AU - Sánchez-Iranzo, Héctor AU - Halavatyi, Aliaksandr AU - Diz-Muñoz, Alba A2 - Bronner, Marianne E VL - 11 PY - 2022 DA - 2022/06/06 SP - e75429 C1 - eLife 2022;11:e75429 DO - 10.7554/eLife.75429 UR - https://doi.org/10.7554/eLife.75429 AB - Development of multicellular organisms requires the generation of gene expression patterns that determines cell fate and organ shape. Groups of genetic interactions known as Gene Regulatory Networks (GRNs) play a key role in the generation of such patterns. However, how the topology and parameters of GRNs determine patterning in vivo remains unclear due to the complexity of most experimental systems. To address this, we use the zebrafish notochord, an organ where coin-shaped precursor cells are initially arranged in a simple unidimensional geometry. These cells then differentiate into vacuolated and sheath cells. Using newly developed transgenic tools together with in vivo imaging, we identify jag1a and her6/her9 as the main components of a Notch GRN that generates a lateral inhibition pattern and determines cell fate. Making use of this experimental system and mathematical modeling we show that lateral inhibition patterning is promoted when ligand-receptor interactions are stronger within the same cell than in neighboring cells. Altogether, we establish the zebrafish notochord as an experimental system to study pattern generation, and identify and characterize how the properties of GRNs determine self-organization of gene patterning and cell fate. KW - notch KW - gene regulatory network KW - notochord KW - lateral inhbition KW - Zebrafish KW - patterning JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -