Biology subjects

Hinman, V.

Publications and source records attributed to Hinman, V..

6 recordsLinked to original sources

bioRxiv2026

A blastema in sea star larvae integrates wound signaling to drive regeneration-specific and developmental gene expression patterns.

Whether regeneration depends on the reactivation of developmental programs, regeneration-specific regulatory mechanisms, or both remains a central question in regeneration biology. Here, we investigate these processes in regenerating larvae of the sea star Patiria miniata, a deuterostome with robust regenerative capacity. By integrating single-nucleus transcriptomics with chromatin accessibility profiling across development and regeneration, we identify a regeneration-induced blastema cell state that is molecularly distinct from pre-existing larval populations and serves as the source of regenerated tissues. We show that regeneration is associated with distinct classes of regeneration-responsive enhancers, including regeneration-specific elements and enhancers reused from development, which link wounding signals to gene regulatory network (GRN) activation. These enhancer classes converge on regulatory programs associated with the transcription factor Runx, positioning Runx as a central node within the inferred regeneration GRN. Notably, we identify a Runx-associated regulatory framework that provides a mechanistic explanation for the de novo emergence of sox4 cells during regeneration through novel deployment of developmentally shared enhancers. Together, our results provide a framework for how wound-induced signals specify regenerative cell states and how regeneration-specific and developmental gene regulatory networks may be coordinated to rebuild lost tissues.

developmental biology↗

bioRxiv2023

Inducible in vivo genome editing in the sea star Patiria miniata

For centuries, echinoderms, a marine-invertebrate phylum, have fascinated scientists for their developmental and postembryonic phenomen. Experimentation on their eggs and embryos in particular have contributed foundation scientific advances. However, powerful molecular genetic studies are restricted to embryonic developmental stages which are amenable to genetic perturbation by microinjection of reagents into the zygotes. This represents a significant bottleneck to the study of postembryonic processes in where the earliest function of a gene must remain intact. We therefore sought to establish a spatio-temporal turnable gene editing tool for these species. Here, using the sea star Patiria miniata as a model we introduce a chemically inducible, Tet-ON, gene expression system. Pairing this Tet-ON system with CRISPR-mediated gene alteration technology we show as a proof-of-principle demonstration an inducible gene editing in the sea star transgenic cell populations for the first time in echinoderm biology. The approach we show here can be adapted for use in other species of echinoderms and will also extend experimental possibilities tremendously.

developmental biology↗

bioRxiv2022

New hypotheses of cell type diversity and novelty from comparative single cell and nuclei transcriptomics in echinoderms

Cell types are the fundamental building blocks of metazoan biodiversity and offer a powerful perspective for inferring evolutionary phenomena. With the development of single-cell transcriptomic techniques, new definitions of cell types are emerging. This allows a conceptual reassessment of traditional definitions of novel cell types and their evolution. Research in echinoderms, particularly sea star and sea urchin embryos have contributed significantly to understanding the evolution of novel cell types, in particular the primary mesenchyme cells (PMCs) and pigment cells that are found in sea urchin but not sea star embryos. This paper outlines the development of a gene expression atlas for the bat star, Patiria miniata, using single nuclear RNA sequencing (snRNA-seq) of embryonic stages. The atlas revealed 22 cell clusters covering all expected cell types from the endoderm, mesoderm and ectoderm germ layers. In particular, four distinct neural clusters, an immune cluster, and distinct right and left coelom clusters were revealed as distinct cell states. A comparison with Strongylocentrotus purpuratus embryo single cell transcriptomes was performed using 1:1 orthologs to anchor and then compare gene expression patterns. S. purpuratus primordial germ cell equivalents were not detected in P. minata, while the left coelom of P. miniata has no equivalent cell cluster in S. purpuratus. Pigment cells of S. purpuratus map to clusters containing immune mesenchyme and neural cells of P. miniata, while the PMCs of S. purpuratus are revealed as orthologous to the right coelom cluster of P. miniata. These results suggest a new interpretation of the evolution of these well-studied cell types and a reflection on the definition of novel cell types.

evolutionary biology↗

bioRxiv2020

Systematic comparison of developmental GRNs explains how novelty is incorporated in early development

The impressive array of morphological diversity among animal taxa represents the product of millions of years of evolution. Morphology is the output of development, therefore phenotypic evolution arises from changes to the topology of the gene regulatory networks (GRNs) that control the highly coordinated process of embryogenesis1. While genetic variation can arise anywhere in the genome and affect any part of an individual GRN, the need to form a viable embryo provides a constraint on the types of variation that pass the filter of selection. A particular challenge in understanding the origins of animal diversity lies in determining how GRNs incorporate novelty while preserving the overall stability of the network, and hence, embryonic viability. Here we assemble a comprehensive GRN, consisting of 42 genes (nodes) and 84 interactions (edges), for the model of endomesoderm specification in the sea star from zygote through gastrulation that corresponds to the GRN for sea urchin development of equivalent territories and stages2. Using these detailed models we make the first systems-level comparison of early development and examine how novelty is incorporated into GRNs. We show how the GRN is resilient to the introduction of a transcription factor, pmar1, the inclusion of which leads to a switch between two stable modes of Delta-Notch signaling. Signaling pathways can function in multiple modes and we propose that GRN changes that lead to switches between modes may be a common evolutionary mechanism for changes in embryogenesis. Our data additionally proposes a model in which evolutionarily conserved network motifs, or kernels, may function throughout development to stabilize these signaling transitions.

developmental biology↗

bioRxiv2019

Developmental transcriptomes of the sea star, Patiria miniata, illuminate the relationship between conservation of gene expression and morphological conservation

Evolutionary changes in developmental gene expression lead to alteration in the embryonic body plan and biodiversity. A promising approach for linking changes in developmental gene expression to altered morphogenesis is the comparison of developmental transcriptomes of closely related and further diverged species within the same phylum. Here we generated quantitative transcriptomes of the sea star, Patiria miniata (P. miniata) of the echinoderm phylum, at eight embryonic stages. We then compared developmental gene expression between P. miniata and the sea urchin, Paracentrotus lividus (~500 million year divergence) and between Paracentrotus lividus and the sea urchin, Strongylocentrotus purpuratus (~40 million year divergence). We discovered that the interspecies correlations of gene expression level between morphologically equivalent stages decreases with increasing evolutionary distance, and becomes more similar to the correlations between morphologically distinct stages. This trend is observed for different sub-sets of genes, from various functional classes and embryonic territories, but is least severe for developmental genes sub-sets. The interspecies correlation matrices of developmental genes show a consistent peak at the onset of gastrulation, supporting the hourglass model of phylotypic stage conservation. We propose that at large evolutionary distance the conservation of relative expression levels for most sets of genes is more related to the required quantities of transcripts in a cell than to conserved morphogenesis processes. In these distances, the information about morphological similarity is reflected mostly in the interspecies correlations between the expressions of developmental control genes.\n\nAuthor summaryUnderstanding the relationship between the interspecies conservation of gene expression and morphological similarity is a major challenge in modern evolutionary and developmental biology. The Interspecies correlations of gene expression levels have been used extensively to illuminate these relationships and reveal the developmental stages that show the highest conservation of gene expression, focusing on the diagonal elements of the correlation matrices. Here we generated the developmental transcriptomes of the sea star, Patiria miniata, and used them to study the interspecies correlations between closely related and further diverged species within the echinoderm phylum. Our study reveals that the diagonal elements of the correlation matrices contain only partial information. The off-diagonal elements, that compare gene expression between distinct developmental stages, indicate whether the conservation of gene expression is indeed related to similar morphology or instead, to general cellular constraints that linger throughout development. With increasing evolutionary distances the diagonal elements decrease and become similar to the off-diagonal elements, reflecting the shift from morphological to general cellular constraints. Within this trend, the interspecies correlations of developmental control genes maintain their diagonality even at large evolutionary distance, and peak at the onset of gastrulation, supporting the hourglass model of phylotypic stage conservation.

evolutionary biology↗

bioRxiv2017

Conserved processes of metazoan whole-body regeneration identified in sea star larvae

BackgroundMetazoan lineages exhibit a wide range of regenerative capabilities that vary among developmental stage and tissue type. The most robust regenerative abilities are apparent in the phyla Cnidaria, Platyhelminthes, and Echinodermata, whose members are capable of whole-body regeneration (WBR). This phenomenon has been well-characterized in planarian and hydra models, but the molecular details of WBR are less established within echinoderms, or any other deuterostome system. Thus, it is not clear to what degree aspects of this regenerative ability are due to deeply conserved mechanisms.\n\nResultsWe characterize regeneration in the larval stage of the Bat Star (Patiria miniata). Following bisection along the anterior-posterior axis, larvae progress through phases of wound healing and re-proportioning of larval tissues. The overall number of proliferating cells is reduced following bisection and we find evidence for a re-deployment of genes with known roles in embryonic axial patterning. Following axial re-specification, we observe a significant localization of proliferating cells to the wound region. Analyses of transcriptome data highlight the molecular signatures of functions that are common to regeneration, including specific signaling pathways and cell cycle controls. Notably, we find evidence for temporal conservation among orthologous genes involved in regeneration from published Platyhelminth and Cnidarian regeneration datasets.\n\nConclusionsThese analyses show that sea star larval regeneration includes phases of wound response, axis respecification, and wound proximal proliferation. Commonalities of the overall process of regeneration, as well as gene usage between this deuterostome and other species with divergent evolutionary origins suggest a deep conservation of whole-body regeneration among the metazoa.

developmental biology↗