Bohm, A. | Search bioRxiv

bioRxiv2023

Unravelling the origins of boldness: A common garden experiment with cave fish (Barbatula barbatula)

Many animals show an aversion to bright, open spaces, with significant variability seen across species, populations, and individuals within populations. Although there is much interest in the underlying causes of this behaviour, few studies have been able to systematically isolate the role of heritable and environmental effects. Here we addressed this gap using a common garden experiment with cave fish. Specifically, we bred and cross-bred cave loaches (Barbatula barbatula) in the lab, raised the offspring in complete darkness or normal light conditions, and studied their light avoidance behaviour. Cave fish spent much more time in a light area and ventured further out, while surface fish spent considerable time on the edge between light and dark areas. Hybrids behaved most similarly to cave fish. Light treatment and eye size and quality only had a modest effect. Our results suggest light avoidance behaviour of cave fish has a heritable basis and is fundamentally linked to increased boldness rather than reduced vision, which is likely adaptive given the complete lack of macropredators in the cave environment. Our study provides novel experimental insights into the behavioural divergence of cave fish and contributes to our broader understanding of the evolution of boldness and behavioural adaptation.

animal behavior and cognition↗

bioRxiv2019

Beyond Conventional Models: Recreating the Initiation, Evolution, and Genome of GBM

BackgroundImagining ways to prevent or treat glioblastoma (GBM) have been hindered by a lack of understanding of its pathogenesis. Although PDGF-AA overexpression may be an early event, critical details of the core biology are lacking. Existing PDGF-driven models replicate its microscopic appearance but not the genomic architecture characteristic of the human disease. Here we report a new model of GBM that overcomes this barrier to authenticity. MethodsUsing a method developed to study neural stem cells, we investigated the effects of PDGF-AA on subventricular zone (SVZ) cells, the putative cell of origin of GBM. We micro-dissected SVZ tissue from p53-null and wild-type adult mice, established primary cultures in media supplemented with PDGF-AA, and assessed cell viability, proliferation, genome stability, and tumour forming potential. ResultsCounterintuitive to its canonical role as a growth factor, we observed immediate and massive death of SVZ cells in PDGF-AA. Wild-type cells did not survive in PDGF-AA. However, a small fraction of null cells evaded apoptosis, displayed attenuated proliferation, gradually accumulated whole chromosome gains and losses, and, signalled by sudden rapid proliferation and growth factor independence, became tumorigenic in immune-competent syngeneic mice. Transformed cells had an OPC-like profile, were resistant to PDGFR- inhibition, and harboured highly abnormal karyotypes similar to those seen in human GBMs. ConclusionThis model associates genome instability in SVZ cells with chronic exposure to PDGF-AA; it is the first model to replicate the genomic landscape of GBM and first in which the earliest phases of GBM can be directly observed. IMPORTANCE OF STUDYWe have developed a mouse model in which the initiation, evolution and genomic landscape of GBM can be thoroughly studied thus paving the way for ideas about how this deadly brain cancer might be prevented, interrupted at an occult stage, or treated with very different therapies.

cancer biology↗