Comparative Analysis of Temperature-Dependent Endocytic Regulation of Notch Signaling in Chick and Mouse Neural Progenitors

Abstract

Introduction: Temperature plays a crucial role in embryonic development, particularly in oviparous species that experience natural fluctuations during incubation. Unlike viviparous embryos developing under stable maternal conditions, chick embryos are exposed to external temperature variability that can influence cellular regulatory processes. Notch signaling, a conserved pathway essential for maintaining the neural progenitor cell (NPC) pool, is regulated by endosomal recycling; however, the mechanism by which temperature modulates this process across species remains poorly understood. Methods: To model environmental challenges experienced by chick embryos, we examined the effects of a physiologically relevant low temperature (30 degrees C) on Dll1-mediated Notch signaling in chick and mouse NPCs. Results: Under hypothermic conditions, Dll1 reporter signals increased in chick NPCs but decreased in mouse NPCs, correlating with corresponding changes in Notch activity. Chick NPCs maintained progenitor gene expression at low temperature, whereas mouse NPCs showed reduced expression. Mechanistic analyses revealed that distinct recycling pathways are differentially required for Notch signaling across temperatures and species. Chick NPCs maintained Notch signaling through both fast recycling (FR) and slow recycling (SR) under normothermia and additional degradation under hypothermia, whereas mouse NPCs relied on SR and degradation under normothermia and showed impaired recycling under hypothermia. Conclusion: Together, these findings reveal species-specific adaptations in the temperature-dependent endocytic regulation of Notch signaling, highlighting how environmental temperature influences the maintenance of neural progenitors across species.