Systematic modeling-driven experiments identify distinct molecular clockworks underlying hierarchically organized pacemaker neurons.

ABSTRACT: In metazoan organisms, circadian (∼24 h) rhythms are regulated by pacemaker neurons organized in a master-slave hierarchy. Although it is widely accepted that master pacemakers and slave oscillators generate rhythms via an identical negative feedback loop of transcription factor CLOCK (CLK) and repressor PERIOD (PER), their different roles imply heterogeneity in their molecular clockworks. Indeed, in Drosophila, defective binding between CLK and PER disrupts molecular rhythms in the master pacemakers, small ventral lateral neurons (sLNvs), but not in the slave oscillator, posterior dorsal neuron 1s (DN1ps). Here, we develop a systematic and expandable approach that unbiasedly searches the source of the heterogeneity in molecular clockworks from time-series data. In combination with in vivo

SUBMITTER: Jeong EM 

PROVIDER: S-EPMC8872709 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature