Biology subjects

Streelman, J. T.

Publications and source records attributed to Streelman, J. T..

11 recordsLinked to original sources

bioRxiv2026

Evolutionarily informed gene sets reveal conserved and lineage-modified transcriptional programs during vertebrate forebrain evolution

The vertebrate forebrain exhibits striking diversity in anatomical architecture, yet is built from deeply conserved gene regulatory programs and cell types that underlie shared neural functions and behaviors. Understanding how these conserved cellular programs are maintained and modified across [~]500 million years of vertebrate evolution requires systematic cross-species single-cell comparisons, a challenge compounded by complex gene evolutionary histories that constrain joint analyses to shared one-to-one orthologs. Here we derive evolutionarily informed gene sets from a global homology graph and represent cells in a shared, interpretable gene-set feature space. Applying this framework to forebrain profiles from eleven vertebrate species, from sea lamprey to human, we construct a unified cross-vertebrate cell atlas. We find that conserved transcriptional programs define stable cell-type identities across vertebrates, with evolutionary divergence occurring predominantly within, rather than between, cell types. Gene-set conservation scales with evolutionary age, whereas lineage-modified programs reflect coordinated clade-level remodeling. Radial glia exhibit a conserved fate bifurcation into neurogenic and gliogenic trajectories with lineage-dependent modulation of transcriptional dynamics. Finally, human neuropsychiatric GWAS signals map onto conserved neural substrates across vertebrates. Together, our results demonstrate that vertebrate forebrain evolution proceeds through lineage-specific tuning of deeply conserved transcriptional programs embedded within stable cellular architectures.

evolutionary biology↗

bioRxiv2026

Cellular basis of accelerated whole-tooth regeneration

Teeth are ectodermal organs that have, throughout their long evolutionary history, retained the capacity for full regeneration and replacement, even in adult stages. Yet, because most mammals (e.g., humans, mice) lack lifelong dental replacement, we do not fully understand its tempo and mode, and we do not have a clear picture of the cell populations and signals that contribute to the process. Here, we used cichlid fishes from Lake Malawi, species that differ in tooth formula (tooth shape and number) but share one-for-one tooth replacement, to (i) explore the tempo of dental replacement after plucking and then (ii) identify the cell populations, gene expression signatures, and interactions between cell populations that change in this plucking paradigm. We observed that cichlid species with divergent dentitions accelerated tooth replacement >3x on the plucked half of the jaw. Then, we used single-nucleus RNA-seq to profile cellular and molecular changes across the first week of post-plucking tooth replacement. This approach allowed us to infer cellular trajectories in dental epithelium and mesenchyme that underlie tooth regeneration. We identifed distinct gene expression profiles and cellular interactions across four time points of accelerated tooth replacement, with divergent involvement of epithelial, mesenchymal and immune cell types. Diferential signaling of Collagen, BMP, MMP, Semaphorin and Slit-Robo pathways was evident after plucking and highlights temporally-sequenced roles of immune response, odontogenesis, vascularization and nerve pathfinding as teeth are constructed anew. Overall, this study provides insight into the trajectory of cellular interactions accompanying whole-tooth replacement and offers a comparative foundation for understanding dental regeneration in vertebrates.

developmental biology↗

bioRxiv2024

Large inversions in Lake Malawi cichlids are associated with habitat preference, lineage, and sex determination

Chromosomal inversions are an important class of genetic variation that link multiple alleles together into a single inherited block that can have important e7ects on fitness. To study the role of large inversions in the massive evolutionary radiation of Lake Malawi cichlids, we used long-read technologies to identify four single and two tandem inversions that span half of each respective chromosome, and which together encompass over 10% of the genome. Each inversion is fixed in one of the two states within the seven major ecogroups, suggesting they played a role in the separation of the major lake lineages into specific lake habitats. One exception is within the benthic sub-radiation, where both inverted and non-inverted alleles continue to segregate within the group. The evolutionary histories of three of the six inversions suggest they transferred from the pelagic Diplotaxodon group into benthic ancestors at the time the benthic sub-radiation was seeded. The remaining three inversions are found in a subset of benthic species living in deep waters. We show that some of these inversions are used as XY sex-determination systems but are also likely limited to a subset of total lake species. Our work suggests that inversions have been under both sexual and natural selection in Lake Malawi cichlids and that they will be important to understanding how this adaptive radiation evolved.

evolutionary biology↗

bioRxiv2024

Adult sex change leads to extensive forebrain reorganization in clownfish

Sexual differentiation of the brain occurs in all major vertebrate lineages but is not well understood at a molecular and cellular level. Unlike most vertebrates, sex-changing fishes have the remarkable ability to change reproductive sex during adulthood in response to social stimuli, offering a unique opportunity to understand mechanisms by which the nervous system can initiate and coordinate sexual differentiation. This study explores sexual differentiation of the forebrain using single nucleus RNA-sequencing in the anemonefish Amphiprion ocellaris, producing the first cellular atlas of a sex-changing brain. We uncover extensive sex differences in cell type-specific gene expression, relative proportions of cells, baseline neuronal excitation, and predicted inter-neuronal communication. Additionally, we identify the cholecystokinin, galanin, and estrogen systems as central molecular axes of sexual differentiation. Supported by these findings, we propose a model of neurosexual differentiation in the conserved vertebrate social decision-making network spanning multiple subtypes of neurons and glia, including neuronal subpopulations within the preoptic area that are positioned to regulate gonadal differentiation. This work deepens our understanding of sexual differentiation in the vertebrate brain and defines a rich suite of molecular and cellular pathways that differentiate during adult sex change in anemonefish. Significance StatementThis study provides key insights into brain sex differences in sex-changing anemonefish (Amphiprion ocellaris), a species that changes sex in adulthood in response to the social environment. Using single nucleus RNA-sequencing, the study provides the first brain cellular atlas showing sex differences in two crucial reproductive areas: the preoptic area and telencephalon. The research identifies notable sex-differences in cell-type proportions and gene expression, particularly in radial glia and glutamatergic neurons that co-express the neuropeptide cholecystokinin. It also highlights differences in preoptic area neurons likely involved in gonadal regulation. This work deepens our understanding of sexual differentiation of the brain in vertebrates, especially those capable of adult sex change, and illuminates key molecular and cellular beginning and endpoints of the process.

neuroscience↗

bioRxiv2023

Natural variation in oxytocin receptor signaling causes widespread changes in brain transcription: a link to the natural killer gene complex

Oxytocin (OXT) is a highly conserved neuropeptide that modulates social cognition, and genetic variation in its receptor gene (Oxtr) is linked to divergent social phenotypes. However, the molecular mechanisms connecting Oxtr genotype to behavioral outcomes remain obscure. Here, we leverage naturally occurring Oxtr polymorphisms in the prairie vole that associate with striatal-specific OXTR density to investigate how OXTR signaling influences brain function. Specifically, we identify OXTR-dependent transcriptomic changes in the natural killer gene complex (NKC) - a genomic region classically associated with peripheral immune function. Centrally, OXTR-regulated NKC genes are positioned to influence microglia-neuron interactions. Consistent with a role for these genes in shaping neuronal connectivity, we show that genetic reduction of OXTR levels leads to increased dendritic spine density on striatal Oxtr-expressing neurons. In addition, we provide support for a similar relation between variation in OXTR mRNA levels and NKC transcription in humans. Together, our findings suggest a role for OXTR signaling in the shaping of neural circuits through transcriptional control of the NKC, outlining a mechanism via which variation in OXTR signaling may influence circuit connectivity to generate diversity in social behaviors.

neuroscience↗

bioRxiv2023

Spatially resolved cell atlas of the teleost telencephalon and deep homology of the vertebrate forebrain

The telencephalon has undergone remarkable diversification and expansion throughout vertebrate evolution, exhibiting striking differences in structural and functional complexity. Nevertheless, fundamental features are shared across vertebrate taxa, such as the presence of distinct regions including the pallium, subpallium, and olfactory structures. Teleost fishes have a uniquely everted telencephalon, which has made it challenging to compare brain regions in fish to those in other vertebrates. Here we combine spatial transcriptomics and single-nucleus RNA-sequencing to generate a spatially-resolved transcriptional atlas of the cichlid fish telencephalon. We then compare cell-types and anatomical regions in the cichlid telencephalon with those in amphibians, reptiles, birds, and mammals. We uncover striking transcriptional similarities between cell populations in the fish telencephalon and subpallial, hippocampal, and cortical cell populations in tetrapods. Ultimately, our work lends new insights into the organization and evolution of conserved cell-types and regions in the vertebrate forebrain.

neuroscience↗

bioRxiv2022

Cellular profiling of a recently-evolved social behavior

Social behaviors are essential for survival and reproduction and vary within and among species. We integrate single nucleus RNA-sequencing (snRNA-seq), comparative genomics, and automated behavior analysis to investigate a recently-evolved social "bower building" behavior in Lake Malawi cichlid fishes. We functionally profile telencephalic nuclei matched to 38 paired behaving/control individuals. Our data suggest bower behavior has evolved in part through divergence in a gene module selectively expressed in a subpopulation of glia lining the pallium. Downregulation of the module is associated with glial departure from quiescence and rebalancing of neuronal subpopulation proportions in the putative homologue of the hippocampus. We show further evidence that behavior-associated excitation of neuronal populations that project to the putative hippocampus mediate glial function and rebalancing. Our work suggests that bower behavior has evolved through changes in glia and region-specific neurogenesis, and more broadly shows how snRNA-seq can generate insight into uncharted behaviors and species.

neuroscience↗

bioRxiv2020

Genome-enabled inference of functional genetic variants in the face, brain and behavior

Lake Malawi cichlid fishes exhibit extensive divergence in form and function among closely related species separated by a relatively small number of genetic changes. During the past million years, hundreds of species have diversified along an ecological axis in rock vs. sand habitats. We compared the genomes of rock- and sand-dwelling species and asked which genetic variants in which genes differed among the groups. We found that 96% of differentiated variants reside in non-coding sequence but these non-coding diverged variants are evolutionarily conserved. The majority of divergent coding variants are missense and/or loss of function. Regions near differentiated variants are enriched for craniofacial, neural and behavioral functional categories. To follow up experimentally, we used rock- vs. sand-species and their hybrids to (i) clarify the push-pull roles of BMP signaling and irx1b in the specification of forebrain territories during gastrulation and (ii) reveal striking context-dependent brain gene expression during adult social behavior. Our results suggest compelling ties between early brain development and adult behavior and highlight the promise of evolutionary reverse genetics - the identification of functional variants from genome sequencing in natural populations.

evolutionary biology↗

bioRxiv2020

Automated measurement of long-term bower behaviors in Lake Malawi cichlids using depth sensing and action recognition

Measuring naturalistic behaviors in laboratory settings is difficult, and this hinders progress in understanding decision-making in response to ecologically-relevant stimuli. In the wild, many animals manipulate their environment to create architectural constructions, which represent a type of extended phenotype affecting survival and/or reproduction, and these behaviors are excellent models of goal-directed decision-making. Here, we describe an automated system for measuring bower construction in Lake Malawi cichlid fishes, whereby males construct sand structures to attract mates through the accumulated actions of thousands of individual sand manipulation decisions over the course of many days. The system integrates two orthogonal methods, depth sensing and action recognition, to simultaneously measure the developing bower structure and classify the sand manipulation decisions through which it is constructed. We show that action recognition accurately (>85%) classifies ten sand manipulation behaviors across three different species and distinguishes between scooping and spitting events that occur during bower construction versus feeding. Registration of depth and video data streams enables topographical mapping of these behaviors onto a dynamic 3D sand surface. The hardware required for this setup is inexpensive (<$250 per setup), allowing for the simultaneous recording from many independent aquariums. We further show that bower construction behaviors are non-uniform in time, non-uniform in space, and spatially repeatable across trials. We also quantify a unique behavioral phenotype in interspecies hybrids, wherein males sequentially express both phenotypes of behaviorally-divergent parental species. Our work demonstrates that simultaneously tracking both structure and behavior provides an integrated picture of long-term goal-directed decision-making in a naturalistic, dynamic, and social environment.

animal behavior and cognition↗

bioRxiv2019

Microhabitat predicts species differences in exploratory behavior in Lake Malawi cichlids

Encountering and adaptively responding to unfamiliar or novel stimuli is a fundamental challenge facing animals and is linked to fitness. Behavioral responses to novel stimuli, or exploratory behavior, can differ strongly between closely related species; however, the ecological and evolutionary factors underlying these differences are not well understood, in part because most comparative investigations have focused on only two species. In this study, we investigate exploratory behavior across 23 species in a previously untested vertebrate system, Lake Malawi cichlid fishes, which comprises hundreds of phenotypically diverse species that have diverged in the past one million years. We investigate behavioral variation across species, across microhabitats, and across environmental contexts. We find strong species differences in behavior that are associated with microhabitat, demonstrate that intermediate microhabitats are associated with higher levels of exploratory behavior, show that patterns of behavioral covariation across contexts are characteristic of modular complex traits, and contrast Malawi cichlid data with behavioral data from selectively bred high-and low-exploratory zebrafish. Taken together, our results tie ecology to species differences in behavior, and highlight Lake Malawi cichlids as a powerful system for understanding the evolution, ecology, and biology of natural behavioral variation. HighlightsO_LIMalawi cichlids exhibit high phenotypic variance in exploratory behaviors C_LIO_LISpecies differences in exploratory behavior are explained by microhabitat C_LIO_LIRock-dwelling species exhibit strong edge preferences across assays C_LIO_LIIntermediate habitats are associated with "high exploratory" open field behavior C_LIO_LIPatterns of behavioral covariance across contexts are modular in Malawi cichlids C_LI

animal behavior and cognition↗

bioRxiv2017

Genome-wide protein phylogenies for four African cichlid species

BackgroundThe thousands of species of closely related cichlid fishes in the great lakes of East Africa are a powerful model for understanding speciation and the genetic basis of trait variation. Recently, the genomes of five species of African cichlids representing five distinct lineages were sequenced and used to predict protein products at a genome-wide level. Here we characterize the evolutionary relationship of each cichlid protein to previously sequenced animal species.\n\nResultsWe used the Treefam database, a set of preexisting protein phylogenies built using 109 previously sequenced genomes, to identify Treefam families for each protein annotated from four cichlid species: Metriaclima zebra, Astatotilapia burtoni, Pundamilia nyererei and Neolamporologus brichardi. For each of these Treefam families, we built new protein phylogenies containing each of the cichlid protein hits. Using these new phylogenies we identified the evolutionary relationship of each cichlid protein to its nearest human and zebrafish protein. This data is available either through download or through a webserver we have implemented.\n\nConclusionThese phylogenies will be useful for any cichlid researchers trying to predict biological and protein function for a given cichlid gene, understanding the evolutionary history of a given cichlid gene, identifying recently duplicated cichlid genes, or performing genome-wide analysis in cichlids that relies on using databases generated from other species.

genomics↗