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Strength of interactions in the Notch gene regulatory network determines patterning and fate in the notochord

Sánchez-Iranzo, Héctor ORCID iD icon 1; Halavatyi, Aliaksandr; Diz-Muñoz, Alba
1 Institut für Biologische und Chemische Systeme (IBCS), Karlsruher Institut für Technologie (KIT)

Abstract:

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.


Verlagsausgabe §
DOI: 10.5445/IR/1000152242
Veröffentlicht am 03.11.2022
Originalveröffentlichung
DOI: 10.7554/eLife.75429
Scopus
Zitationen: 1
Dimensions
Zitationen: 3
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Biologische und Chemische Systeme (IBCS)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2022
Sprache Englisch
Identifikator ISSN: 2050-084X
KITopen-ID: 1000152242
HGF-Programm 47.14.02 (POF IV, LK 01) Information Storage and Processing in the Cell Nucleus
Erschienen in eLife
Verlag eLife Sciences Publications
Band 11
Seiten Art.-Nr.: e75429
Vorab online veröffentlicht am 06.06.2022
Schlagwörter developmental biology, notch, gene regulatory network, notochord, lateral inhbition, zebrafish, patterning
Nachgewiesen in Scopus
Web of Science
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