UC San Diego

Amphibian metamorphosis is a transitional period that involves significant changes in the cell type populations and biological processes occurring in the brain. However, gene expression dynamics during this process are not as well-studied as they are in earlier development. To rectify this, we sought to quantify gene expression in the X. laevis brain over this time period in two ways: firstly over stages of development in the midbrain, and secondly across regions of the brain at a single developmental stage. We found that genes pertaining to positive regulation of neuronal proliferation as well as known progenitor cell markers were upregulated prior to metamorphic climax in the midbrain; concurrently, expression of cell cycle timing regulators decreased in expression across this period, supporting the notion that cell cycle lengthening contributes to a decrease in proliferation by the end of metamorphosis. We also found that at the start of metamorphosis, neural progenitor populations appeared to be similar across the fore-, mid-, and hindbrain. Genes pertaining to negative regulation of differentiation were upregulated in the spinal cord compared to the rest of the brain, however, suggesting that a different program of neurogenesis regulation may be occurring there. Finally, we found that regulation of biological processes like cell fate commitment and synaptic signaling follow similar trajectories in the brain across early tadpole metamorphosis and mid- to late-embryonic mouse development. By comparing expression across both temporal and spatial conditions, we were able to illuminate cell type and biological pathway dynamics in the brain during metamorphosis.