Developmental function and state transitions of a gene expression oscillator in Caenorhabditis elegans

Abstract

Gene expression oscillators can structure biological events temporally and spatially. Different biological functions benefit from distinct oscillator properties. Thus, finite developmental processes rely on oscillators that start and stop at specific times, a poorly understood behavior. Here, we have characterized a massive gene expression oscillator comprising > 3,700 genes in Caenorhabditis elegans larvae. We report that oscillations initiate in embryos, arrest transiently after hatching and in response to perturbation, and cease in adults. Experimental observation of the transitions between oscillatory and non-oscillatory states at high temporal resolution reveals an oscillator operating near a Saddle Node on Invariant Cycle (SNIC) bifurcation. These findings constrain the architecture and mathematical models that can represent this oscillator. They also reveal that oscillator arrests occur reproducibly in a specific phase. Since we find oscillations to be coupled to developmental processes, including molting, this characteristic of SNIC bifurcations endows the oscillator with the potential to halt larval development at defined intervals, and thereby execute a developmental checkpoint function.

Temporal scaling inC. eleganslarval development

“…In addition, the seam cells V1-V4 and V6 undergo an additional symmetric division in the L2 larval stage, doubling their number. Oscillatory gene expression is a pervasive phenomenon in C. elegans, with thousands of gene transcripts oscillating during development with a periodicity corresponding to that of the molting cycle [12][13][14]. Here, we focused on the oscillatory gene wrt-2, a hedgehog-like protein expressed in seam cells, that peaks in expression once every larval stage [12,21]…”

“…However, more recent measurements disputed the key assumption that all processes follow the same Arrhenius equation [48,49] On the molecular level, developmental timing is thought to be controlled either by oscillators or 'hourglass' mechanisms. In C. elegans, even though there is now evidence both for hourglass mechanisms [16,17] and oscillators [11,14] in regulating timing of larval development, we still do not understand how the exact time at which cell-level events are initiated is determined on the molecular level. Both hourglass and oscillator mechanisms do not exhibit temporal scaling of their decay time or period, respectively, without alterations to their basic mechanism.…”

“…There is a clear periodic aspect to C. elegans development, with molts occurring every 8-10 hours at 25˚C. Moreover, larval stages are accompanied by genome-wide oscillatory expression of a multitude of genes, with peaks occurring once per larval stage [12][13][14].…”

Tissue-Specific Transcription Footprinting Using RNA PoI DamID (RAPID) in Caenorhabditis elegans

“…In a postmitotic context, however, RAPID should be able to identify transcriptional upregulation events in response to environmental changes, as successfully achieved in Drosophila ( Widmer et al 2018 ). In addition, recent publications have highlighted the existence of a large cohort of genes with oscillating expression between molts ( Kim et al 2013 ; Hendriks et al 2014 ; Hutchison et al 2020 ; Meeuse et al 2020 ). RAPID is unlikely to capture this type of phenomenon, which could turn into a desirable feature when one wants to mitigate this variability, e.g.…”

Differential regulation of developmental stages supports a linear model forC. eleganspostembryonic development

“…The repetitive process of molting is coupled to oscillatory expression of ~3,700 genes (Hendriks et al, 2014; Kim et al, 2013; Meeuse et al, 2020). One of the oscillating genes is lin-42 , the homologue of the Drosophila melanogaster clock protein period (Jeon et al, 1999).…”