Silvius, K. M. | bioRxiv Science

bioRxiv2022

Zebrafish her3 knockout impacts developmental and cancer-related gene signatures

HES3 is a basic helix-loop-helix transcription factor that regulates neural stem cell renewal during development. HES3 overexpression is predictive of reduced overall survival in patients with fusion-positive rhabdomyosarcoma, a pediatric cancer that resembles immature and undifferentiated skeletal muscle. However, the mechanisms of HES3 cooperation in fusion-positive rhabdomyosarcoma are unclear and are likely related to her3/HES3s role in neurogenesis. To investigate HES3s function during development, we generated a zebrafish CRISPR/Cas9 knockout of her3, the zebrafish ortholog of HES3. Loss of her3 is not embryonic lethal and adults exhibit expected Mendelian ratios. Embryonic her3 zebrafish mutants are significantly smaller than wildtype and a subset present with lens defects as adults. Transcriptomic analysis of her3 mutant embryos indicates that genes involved in organ development, such as pctp and grinab, are significantly downregulated. Further, differentially expressed genes in her3 knockout embryos are enriched for HOX and SOX10 motifs. Several cancer-related gene pathways are impacted, including the inhibition of matrix metalloproteinases. Altogether, this new model is a powerful system to study her3/HES3-mediated neural development and its misappropriation in cancer contexts. Summary StatementHere, we generate and characterize a zebrafish her3/HES3 knockout to elucidate the functional role of her3/HES3, a transcriptional repressor, in neural development and tumorigenic processes.

developmental biology↗

bioRxiv2020

Mysterious disappearances of a large mammal in Neotropical forests

The drivers of periodic population cycling by some animal species in northern systems remain unresolved1. Mysterious disappearances of populations of the Neotropical, herdforming white-lipped peccary (Tayassu pecari, henceforth "WLP") have been anecdotally documented and explained as local events resulting from migratory movements or overhunting2,3,4, or as disease outbreaks5,6, and have not been considered in the context of large-scale species-specific population dynamics. Here we present evidence that WLP disappearances represent troughs in population cycles that occur with regular periodicity and are synchronized at regional and perhaps continent-wide spatial scales. Analysis of 43 disappearance events and 88 years of commercial and subsistence harvesting data reveals boom - bust population cycles lasting from 20 to 30 years, in which a rapid population crash occurring over 1 to 5 years is followed by a period of absence of 7 to12 years and then a slow growth phase. Overhunting alone cannot explain the crashes, but as in northern systems dispersal during the growth phase appears to play a key role. This is the first documentation of population cycling in a tropical vertebrate.

ecology↗