BLMP-1 is a critical temporal regulator of dietary-restriction-induced response in Caenorhabditis elegans

Abstract

The extrinsic diet and the intrinsic developmental programs are intertwined. Although extensive research has been conducted on how nutrition regulates development, whether and how developmental programs control the timing of nutritional responses remain barely known. Here, we report that a developmental timing regulator, BLMP-1/BLIMP1, governs the temporal response to dietary restriction (DR). At the end of larval development, BLMP-1 is induced and interacts with DR-activated PHA-4/FOXA, a key transcription factor responding to the reduced nutrition. By integrating temporal and nutritional signaling, the DR response regulates many development-related genes, including gska-3/GSK3β, through BLMP-1-PHA-4 at the onset of adulthood. Upon DR, a precocious activation of BLMP-1 in early larval stages impairs neuronal development through gska-3, whereas the increase of gska-3 by BLMP-1-PHA-4 at the last larval stage suppresses WNT signaling in adulthood for DR-induced longevity. Our findings reveal a temporal checkpoint of the DR response that protects larval development and promotes adult health.