Biology subjects

Hagen, O.

Publications and source records attributed to Hagen, O..

6 recordsLinked to original sources

bioRxiv2026

Optic nerve innervation promotes Wnt/b-catenin pathway activity and progenitor cell proliferation in the zebrafish optic tectum

In the zebrafish visual system, accurate retinotopic mapping occurs throughout life as new neurons are generated and integrated into existing circuitry in both the retina and optic tectum (OT). To explore how OT development changes relative to innervation from the retina, we examined cell death and proliferation in genetic and surgical models that disrupt retinal innervation of the OT. Specifically, we compared lakritz (lak) mutants, which have no optic nerves due to a lesion in the atoh7 gene, with either wild-type or one-eyed fish generated through surgical eye removal. We observed elevated cell death, fewer proliferating progenitors, and fewer sox2+ OT neuroepithelial stem cells in lak mutant and denervated OT lobes. To examine whether light-mediated vision contributes to proliferation and survival in the optic tectum, we reared fish in constant darkness and then compared survival and proliferation of OT cells in innervated and non-innervated tecta. We found that OT cells were still more likely to survive and proliferate in the presence of optic nerve innervation even when fish were reared in the dark. To identify molecular pathways that could regulate OT growth, we examined the expression of known mitogens in the zebrafish optic tectum and found evidence that Wnt/{beta}-catenin pathway activity could promote innervation-dependent proliferation in lak mutant tecta. Expression of both wnt3a and the Wnt/{beta}-catenin target gene axin2, as detected by in situ hybridization and RT-qPCR, is decreased in non-innervated tectal lobes. Further supporting an innervation-dependent role for Wnt/{beta}-catenin pathway activation in the zebrafish OT, we found that lak mutants treated with a Wnt-pathway agonist, BIO, exhibited levels of OT cell proliferation that were indistinguishable from wild-type. Together these findings suggest that progenitor cells in the optic tectum produce Wnt3a in response to innervation by the optic nerve, providing new insight into how a vertebrate visual system coordinates growth across its sensory and recipient tissues.

Developmental Biology↗

bioRxiv2026

Unexpected global biodiversity responses to climate change arise from complex adaptation, seascape, and dispersal dynamics

Global marine biodiversity peaks in the tropics and is widely projected to shift polewards under climate warming as species track thermal optima. These projections rely largely on phenomenological models that treat species responses as shifts in climate suitability and neglect fundamental eco-evolutionary dynamics. The consequences of these dynamics in fluctuating populations for global biodiversity patterns therefore remain unresolved. We addressed this deficit by integrating local adaptation, dispersal, and gene flow - mediated trait homogenisation into spatially explicit global simulations of >1,400 tropical reef fishes under climate change. Biodiversity responses departed systematically from simple poleward redistribution. Depending on the interaction between dispersal and adaptive capacity, latitudinal richness peaks widened or narrowed, shifted equatorward or poleward, or collapsed entirely. These alternative regimes emerged from threshold-dependent interactions between seascape connectivity, metapopulation trait homogenisation, and accumulating thermal stress. Critically, greater dispersal enhanced persistence only below seascape-driven connectivity thresholds; beyond which homogenisation of traits across thermally heterogeneous populations disrupted local adaptation - particularly at metapopulation peripheries - and increased extinction risk. Continuous demographic feedback further generated cumulative stress and extinction tipping dynamics absent from snapshot suitability models. Our results show that eco-evolutionary dynamics can invert or destabilise expected climate-driven redistribution patterns, indicating that projections excluding these mechanisms may systematically misestimate the magnitude and direction of global biodiversity change in a rapidly warming ocean.

ecology↗

bioRxiv2021

South American freshwater fish diversity shaped by Andean uplift since the Late Cretaceous

South America is home to the highest freshwater fish biodiversity on Earth1,2. The hotspot of species richness is located in the western Amazon Basin, and richness decreases downstream along the Amazon River towards the mouth at the Atlantic coast (Fig. 1b, c)3,4, which contradicts the positive relationship between stream size and biodiversity that is commonly observed in river systems across the world5,6. We investigate the role of river rerouting events caused by Andean mountain building and repeated episodes of flooding in western Amazonia in shaping the modern-day richness pattern of freshwater fishes in South America. To this end, we combine a reconstruction of river networks following Andean surface uplift since 80 million years ago with a mechanistic biological model simulating dispersal, allopatric speciation and extinction over the dynamic landscape of rivers and lakes. We show that the numerous small river rerouting events in western Amazonia resulting from mountain building produced highly dynamic riverine habitats that caused high diversification rates, shaping the exceptional present-day richness of this region. The history of marine incursions and lakes, including the Miocene Pebas megawetland system in western Amazonia, played a secondary role. This study is a major step towards the understanding of the processes involved in the interactions between the solid Earth, landscapes, and life of extraordinary biodiverse South America. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/444133v1_fig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@c4643forg.highwire.dtl.DTLVardef@1916aa5org.highwire.dtl.DTLVardef@1f0900forg.highwire.dtl.DTLVardef@81ea9b_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFig. 1.C_FLOATNO a, Major rivers and drainage basins of South America. HydroRIVERS data from the HydroSHEDS database17; rivers shown that drain a surface area of >4000 km2. b, Freshwater fish species richness per sub-basin (level 5 HydroBASINS17), reproduced from data from Cassemiro, et al. 4. c and d, Richness versus distance to outlet per sub-basins (as shown in panel b), illustrating the positive relationship (richness decreases towards the mouth of the river) for the Amazon (c), and, for comparison, a negative relationship for the Parana-Paraguay river basin (d). C_FIG

evolutionary biology↗

bioRxiv2021

gen3sis: the general engine for eco-evolutionary simulations on the origins of biodiversity

Understanding the origins of biodiversity has been an aspiration since the days of early naturalists. The immense complexity of ecological, evolutionary and spatial processes, however, has made this goal elusive to this day. Computer models serve progress in many scientific fields, but in the fields of macroecology and macroevolution, eco-evolutionary models are comparatively less developed. We present a general, spatially-explicit, eco-evolutionary engine with a modular implementation that enables the modelling of multiple macroecological and macroevolutionary processes and feedbacks across representative spatio-temporally dynamic landscapes. Modelled processes can include environmental filtering, biotic interactions, dispersal, speciation and evolution of ecological traits. Commonly observed biodiversity patterns, such as , {beta} and {gamma} diversity, species ranges, ecological traits and phylogenies, emerge as simulations proceed. As a case study, we examined alternative hypotheses expected to have shaped the latitudinal diversity gradient (LDG) during the Earths Cenozoic era. We found that a carrying capacity linked with energy was the only model variant that could simultaneously produce a realistic LDG, species range size frequencies, and phylogenetic tree balance. The model engine is open source and available as an R-package, enabling future exploration of various landscapes and biological processes, while outputs can be linked with a variety of empirical biodiversity patterns. This work represents a step towards a numeric and mechanistic understanding of the physical and biological processes that shape Earths biodiversity.

evolutionary biology↗

bioRxiv2021

Species ecology explains the various spatial components of genetic diversity in tropical reef fishes

Intraspecific genetic diversity should be dependent on species ecology, but the influence of ecological traits on interspecific differences in genetic variation is yet to be explored. Generating sequenced data for 20 tropical reef fish species of the Western Indian Ocean, we investigate how species ecology influences genetic diversity patterns from local to regional scales. We distinguish between the , {beta} and{gamma} components of genetic diversity, which we subsequently link to six ecological traits. In contrast to what is expected by the neutral theory of molecular evolution, we find that the and{gamma} components of genetic diversity are negatively associated with species abundance, which can be explained by larger variance in reproductive success in large populations and/or higher introgression in less frequent species. Pelagic larval duration, an important dispersal trait in marine fishes, is found to be negatively related to genetic {beta} diversity, as expected by theory. We conclude that the neutral theory of molecular evolution may not be sufficient to explain genetic diversity in tropical reef fishes and that additional processes influence those relationships.

genetics↗

bioRxiv2019

Loss of cell cycle control renders cells nonresponsive to local extrinsic differentiation cues

Objective and approachesAberrantly proliferating cells are linked to a number of diseases including cancers and developmental defects.To determine the extent to which local extrinsic signals contribute to or ameliorate mutant cell behaviors, we examined survival and differentiation of mutant cells in wild-type retinal environments by generating chimeric zebrafish embryos comprised of unlabeled host cells and GFP-labeled neural progenitor donor cells. In addition, we examined the fate of retinal progenitor cells when cdkn1c, a cyclin dependent kinase inhibitor, was induced in clones within wild-type and hdac1 mutant retinae.\n\nResultsWe found that seven of the ten mutants examined exhibited apoptosis when grafted into wild-type tissue, with cells from two slowly cycling mutants, elys and emi1, noticeably differentiating in a wild-type environment. Observations of the one hyperproliferative mutant, hdac1, revealed that these mutant cells did not appear to die or differentiate but instead survived and formed tumor-like rosettes in a wild-type environment. Ectopic expression of cdkn1c was unable to force cell cycle exit and differentiation of the majority of hdac1 mutant cells.\n\nConclusionsTogether, these results suggest that although a wild-type environment rarely encourages cell cycle exit and differentiation of neural progenitors with cell cycle defects, wild-type survival signals may enable hyperproliferative progenitor cells to persist instead of die.

developmental biology↗