Biology subjects

Kann, A. P.

Publications and source records attributed to Kann, A. P..

4 recordsLinked to original sources

bioRxiv2025

Distributed neural computation and the evolution of the first brains

The origin of brains in the Precambrian was a landmark in animal evolution, enabling new behavior and life histories. Brains likely evolved from diffuse nerve nets, but we do not know what the first brains looked like or how they were organized. Acoel worms, the likely sister lineage to all other animals with brains, offer a unique window into this transition. Here, we studied the acoel worm Hofstenia miamia, a marine predator that hunts planktonic invertebrates and displays other sophisticated behavior. We found that H. miamia has an unusual diffuse brain: a subepidermal network of dense neuropil exhibiting little regionalization or stereotypy in gross anatomy or distribution of neural cell types. Remarkably, we found that behavior in H. miamia is robust to large, arbitrary amputations of brain regions, suggesting that most regions can perform most computations. More brain tissue improves performance, especially on challenging tasks, but no specific brain region is required. These results lead us to propose that H. miamias brain is composed of computationally pluripotent "tiles" that interact to generate coherent behavior. This architecture suggests a trajectory for nervous system evolution in which early brains may have arisen through the condensation of diffuse nerve nets into unregionalized brains, with regionalization evolving secondarily.

neuroscience↗

bioRxiv2025

Cooperation between proximate cell layers drives large-scale wound closure prior to whole-body regeneration

Wound closure is an essential aspect of successful regeneration, often acting as the first morphogenetic event that precedes downstream cellular events. Despite heavy investment in studying whole-body regeneration in many invertebrate systems, the steps by which these organisms heal their wounds remain understudied. Here, we investigate the cellular mechanisms of wound healing in the acoel Hofstenia miamia, an invertebrate worm capable of whole-body regeneration. H. miamia have two distinct epithelial layers, an outer epidermis and the epithelial lining of their pharynx. By labeling regenerating fragments with an actin dye, we found that H. miamia use distinct mechanisms of epithelial wound repair across different injury contexts. In transverse wounds that dont injure the pharyngeal epithelium, the epidermis closes by gradual radial constriction. In contrast, injuries that damage both the epidermis and the pharyngeal epithelium show the formation of long, actin-rich protrusions that cross the wound gap and form heterotypic bridges prior to re-epithelialization. Muscle contraction is required for the formation of heterotypic bridges - when animals are anesthetized and immobile, they are unable to form these cellular bridges, and epidermal cells cannot migrate independently. Global actomyosin contractility also plays a role in repair mechanisms, and pharmacological perturbation of contractility shifts the dynamics of wound closure after amputation. In the presence of blebbistatin, heterotypic bridge formation is inhibited but homotypic re-epithelialization is accelerated through increased cell crawling. Together, this work identifies mechanisms by which epithelial layers close large wounds in vivo, identifying novel heterotypic cellular bridges in wound closure and demonstrating the conservation of actin-mediated processes in an early-diverging phylum.

cell biology↗

bioRxiv2024

Reproductive life history of an acoel worm

Acoel worms belong to an enigmatic and understudied animal lineage in the phylum Xenacoelomorpha. Sparse taxonomic and histological work suggests that these worms exhibit a diversity of reproductive anatomies and likely a corresponding diversity in reproductive behavior. Here, we study the reproductive life history of the three-banded panther worm Hofstenia miamia, an acoel that is emerging as a lab-tractable model system. Using confocal microscopy and histology, we describe H. miamias reproductive organs, identifying structures previously unknown in acoels. Following a cohort of worms from zygote to adulthood, we quantify the developmental dynamics of their reproductive organs, and find that these organs emerge in a stereotyped sequence as a function of increasing body size. Studying the dynamics of organ growth and de-growth during regeneration and in starvation, we show that reproductive organs follow similar growth rules in these contexts, suggesting that they are regulated by a size-associated program in all growth contexts. Finally, we study egg-laying behavior, finding that H. miamia lay their eggs through their mouths after loading them into their pharynges. Worms lay eggs for multiple months after a single mating, suggesting long-term sperm storage despite lacking a storage organ; we also find that worms can lay viable eggs without mating, indicating a capacity for self-fertilization. Further, we show that worms assess their environment to make decisions about when and where to lay their eggs, and sometimes lay eggs in communal clutches. Together, our work establishes foundational knowledge to enable the experimental study of reproductive anatomy, physiology, and behavior in acoels.

zoology↗

bioRxiv2022

Rescue of aged muscle stem cell intrinsic quiescence defects by AKT inhibition revealed with a 3D biomimetic culture assay

Adult skeletal muscle harbors a population of muscle stem cells (MuSCs) that are required to repair or reform multinucleated myofibers after tissue injury. In youth, MuSCs return to a reversible state of cell cycle arrest termed quiescence after injury resolution. By contrast, a proportion of MuSCs in aged muscle remain in a semi-activated state, causing a premature response to subsequent injury cues that results in incomplete tissue repair and eventual stem cell depletion. Regulation of the balance between MuSC quiescence and activation in youth and in age may hold the key to restoring tissue homeostasis with age, but is incompletely understood. To fill this gap, we developed a simple and tractable in vitro method, with a 96-well footprint, to rapidly inactivate MuSCs freshly isolated from young skeletal muscle tissue, and return them to a quiescent-like state for at least one-week. This was achieved by introducing MuSCs into a three-dimensional (3D) bioartificial niche comprised of a thin sheet of multinucleated myotubes, which we iterate, and analyze temporally, to show that these in vivo niche features provide the minimal cues necessary to inactivate MuSCs and induce quiescence. By seeding the 3D myotube sheets with different starting numbers of MuSCs, the assay revealed cellular heterogeneity and population-level adaptation activities that converged on a common steady-state niche repopulation density; behaviors previously observed only in vivo. Quiescence-associated hallmarks included a Pax7+CalcR+MyoD- c-FOS- molecular signature, in vivo quiescent-like morphologies including oval-shaped nuclei and long cytoplasmic projections with N-cadherin+ tips, as well as the acquisition of polarized niche markers. Leveraging high-content imaging and bespoke CellProfilerTM-based image analysis pipelines, we demonstrate a relationship between morphology and cell fate signatures opening up the possibility of real-time morphology-based screening. Notably, when MuSCs from aged muscle were introduced into the assay, they displayed aberrant proliferative activities, delayed inactivation kinetics, persistence of activation-associated morphologies, and population depletion; quiescence-associated defects that we show are rescued by wortmannin treatment. Thus, the miniaturized assay offers an unprecedented opportunity to systematically investigate long-standing queries in areas such as regulation of adult stem cell pool size and functional heterogeneity within the MuSC population, and to uncover regulators of quiescence in youth and in age.

bioengineering↗