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Reddien, P.

Publications and source records attributed to Reddien, P..

4 recordsLinked to original sources

Multimodal reference brain atlas of adult Danionella cerebrum

Mechanistic accounts of brain function require a common coordinate system in which structural, molecular and functional data can be integrated and compared across individuals. The teleost genus Danionella is unique among vertebrates in retaining lifelong transparency, allowing non-invasive, cellular-resolution functional imaging across the entire adult brain. A reference atlas in this model would therefore provide a strong foundation for causal and comparative circuit studies. Here we present an integrated anatomical, molecular and functional reference brain for adult Danionella cerebrum as a standardised atlas resource. Using a transgenic nuclear fluorescence marker, whole-mount tissue clearing and high-resolution two-photon microscopy, we generated an average reference brain from 21 adult fish to create a common coordinate system. Whole-mount in situ hybridisation for 29 neuronal markers, complemented by tract annotation from structural imaging and tracer injections, enabled us to segment 203 neuroanatomical regions. We found pronounced sex differences in telencephalic, cerebellar and hindbrain nuclei, revealing sexually dimorphic organisation across multiple brain regions. All data and segmentations are made openly accessible, providing a community resource for studies of circuit function, molecular makeup and sexual dimorphism in an optically accessible adult vertebrate brain.

neuroscience↗

Whole-body single-cell atlas of an adult vertebrate in homeostasis and regeneration

A complete cell-type transcriptome atlas of a vertebrate could promote understanding of animal cell-type composition, organization, and evolution. The miniaturized, transparent, and regenerative teleost Danionella cerebrum brings whole-vertebrate single-cell profiling experiments within reach. We performed region-stratified single-cell RNA sequencing across the adult Danionella body and mapped cell types and gene expression at single-cell resolution using spatial transcriptomics. We delineated spatially-distinct neural cell types based on their regional gene expression signatures. The body-wide atlas elucidated cell types harboring adult positional information, uncovered paedomorphic features, and revealed conserved body-region and appendage-specification programs in adult connective tissue. Comparative analyses revealed conserved neural cell types, and regeneration datasets uncovered expression dynamics during telencephalon regeneration. This whole-vertebrate transcriptome atlas yields a comprehensive resource for myriad questions in biology and neuroscience.

systems biology↗

Spatial gene expression maps in vertebrate limbs display conserved and regenerative species-specific features within connective tissue

Regeneration is widespread but sparsely distributed throughout the animal kingdom. Identifying factors that differentiate regenerative and non-regenerative organisms could enable approaches for improving regenerative outcomes in non-regenerative species. Constitutive adult positional information can be required for regeneration, but has been poorly characterized across animals. Here, we generated positional gene expression atlases for the limbs of one regenerative (axolotl) and one non-regenerative (mouse) vertebrate. Regional gene expression signatures in both species are highly overlapping and mirror multiple developmental positional information patterns, particularly along the primary limb axis. These expression signatures are largely harbored in connective tissue, including diverse fibroblast types, in both organisms. We also identified species-specific regional expression patterns, including for Proxima, a novel gene encoding a secreted factor with strong positional expression in axolotl. Positional gene expression similar to developmental patterns also exists between forelimbs and hindlimbs and along anterior-posterior and dorsal-ventral limb axes, although some of these regional expression signatures are stronger in axolotl than in mouse. This work establishes regional atlases of adult vertebrate limbs and suggests that the connective tissue of regenerative and non-regenerative vertebrate limbs share a conserved signature of positional memory, with some signatures more apparent in the regenerative species.

developmental biology↗

Krüppel-like factor 4 is required for development and regeneration of germline and yolk cells from somatic stem cells in planarians

Sexually reproducing animals segregate their germline from their soma. In addition to gamete-producing gonads, planarian and parasitic flatworm reproduction relies on yolk-cell-generating accessory reproductive organs (vitellaria) supporting development of yolkless oocytes. Despite the importance of vitellaria for flatworm reproduction (and parasite transmission), little is known about this unique evolutionary innovation. Here we examine reproductive system development in the planarian Schmidtea mediterranea, in which pluripotent stem cells generate both somatic and germ cell lineages. We show that a homolog of the pluripotency factor Klf4 is expressed in primordial germ cells, presumptive germline stem cells, and yolk-cell progenitors. klf4 knockdown animals fail to specify or maintain germ cells; surprisingly, they also fail to maintain yolk cells. We find that yolk cells display germ-cell-like attributes and that vitellaria are structurally analogous to gonads. In addition to identifying a new proliferative cell population in planarians (yolk cell progenitors) and defining its niche, our work provides evidence supporting the hypothesis that flatworm germ cells and yolk cells share a common evolutionary origin.

developmental biology↗