Hes7, a negative feedback regulator of notch signaling, is essential for morphogenetic robustness

Author : Md. Nazmul Islam

Abstract :Developmental system is expected to be robust despite environmental fluctuations or internal noise. During embryonic development, Hes7, negative feedback regulator of Notch signaling, orchestrates the temporal and spatial aspects of somite formation and axial skeleton development. However, the developmental consequences of Hes7 haploinsufficiency, characterized by the existence of a single functioning allele, remain unclear. This study aims to investigate the impact of Hes7 heterozygosity on the robustness of somitogenesis and axial skeletal development. Fluorescence in situ hybridization (FISH) was conducted at the somite level where no significant differences were noticed regarding the expression of Uncx4.1, a posterior somite marker, between WT and Hes7+/- embryos, suggesting preserved anterior-posterior (A/P) somite polarity under normal condition. However, significant transcriptional fluctuation of Hes7 was observed between WT and Hes7+/- embryos at the PSM. To investigate the effects of this transcriptional fluctuation, I administered valproic acid (VPA), a known external perturbation, intraperitoneally and found minor skeletal defects in WT neonates whereas Hes7+/- neonates showed severe skeletal abnormalities. At the embryonic stage, more abnormal somites were observed in Hes7+/- embryos compared to WT following VPA treatment. These findings support the hypothesis that one allele missing of Hes7 compromises the robustness of the segmentation clock, rendering somitogenesis more vulnerable to environmental perturbations.

Keywords :Hes7 haploinsufficiency weakens somitogenesis robustness, heightening defects under perturbation.

Conference Name :International Conference on Cell and Developmental Biology (ICCDB-25)

Conference Place Suwon-si, South Korea

Conference Date 26th Aug 2025