We have contributed to a new study mainly run by the lab of Kim Dale published in Genes & Development, titled “NOTCH1 S2513 is critical for the regulation of NICD levels impacting the segmentation clock in hiPSC-derived PSM cells and somitoids”. The work investigates how a mutation in NOTCH1, identified in T-cell acute lymphoblastic lymphoma (T-ALL) patients, affects somitogenesis.
Using human iPSC-derived presomitic mesoderm (PSM) cells and somitoid cultures, the study shows that mutation of NOTCH1 serine 2513 to alanine increases NICD stability, disrupts clock gene oscillations, and impairs somitoid polarization, elongation, and segment formation. These findings reveal a mechanism by which post-translational modification of a key segmentation clock component regulates vertebrate axis segmentation.
Dr. Sonnen’s lab contributed by establishing and analyzing the somitoid cultures, linking experimental biology with theoretical understanding of the segmentation clock dynamics.
Read the full article here.