Biology subjects

Krasovec, G.

Publications and source records attributed to Krasovec, G..

7 recordsLinked to original sources

bioRxiv2025

Multifaceted conserved functions of Notch during post-embryonic neurogenesis in the annelid Platynereis

Notch signaling is an evolutionarily conserved pathway known to orchestrate neurogenesis by regulating the transition of progenitor cells to differentiated neurons and glia, as well as by directing neurite outgrowth and axon guidance in many species. Although extensively studied in vertebrates and ecdysozoans, the role of Notch in spiralians (including mollusks, annelids or flatworms) remains largely unexplored, limiting our understanding of its conserved functions across bilaterians. In this study, we focus on the segmented annelid Platynereis dumerilii, a model organism in neurobiology and regeneration, to investigate Notch signaling functions during post-embryonic developmental processes. We show that Notch pathway components are expressed in neurogenic territories during both posterior elongation and regeneration, two processes requiring sustained neurogenesis. Through chemical inhibitions of the pathway and RNA-seq profiling, we demonstrate that Notch signaling regulates neural progenitor specification, differentiation, and overall neurogenic balance in the regenerating and elongating posterior part. Moreover, disruption of Notch activity leads to severe defects in pygidial and central nervous system organization, including abnormal axon guidance and impaired neurite outgrowth. Altogether, our results support the hypothesis that Notch has multifaceted conserved functions in neurogenesis across bilaterians, shedding light on the ancestral functions of this critical pathway.

developmental biology↗

bioRxiv2025

An unexpected mode of whole-body regeneration from reaggregated cell suspension in Hydractinia (Cnidaria, Hydrozoa)

Hydrozoan cnidarians are among the few animals that can regenerate whole bodies from reaggregated cell dissociations but the cellular and molecular mechanisms that control this ability and how it is related to embryonic development are not well understood. Furthermore, the evolution of this type of regeneration is enigmatic since it does not occur naturally. Here, we show that aggregate regeneration in Hydractinia symbiolongicarpus proceeds through several, consistent stages that include the formation of an epidermal layer, followed by migration, proliferation, and differentiation of adult pluripotent stem cells, known as i-cells. Migration of i-cells is controlled by sphingosine-1-phosphate signaling. Single-cell transcriptomics revealed, surprisingly, that the newly regenerated individual derives nearly exclusively from i-cell progeny rather than from recycled somatic cells, as seen in other hydrozoans. Given the similarity of this phenomenon to embryogenesis, we propose that the ability of Hydractinia cell aggregates to regenerate is a side effect of the animals i-cell-mediated development.

developmental biology↗

bioRxiv2024

A positive feedback loop between germ cells and gonads induces and maintains cnidarian sexual reproduction

The fertile gonad includes cells of two distinct developmental origins: the somatic mesoderm and the germline. How somatic and germ cells interact to develop and maintain fertility is not well understood. Here, using grafting experiments and transgenic reporter animals, we find that a specific part of the gonad-the germinal zone-acts as a sexual organizer to induce and maintain de novo germ cells and somatic gonads in non-sexual tissue in the cnidarian Hydractinia symbiolongicarpus. We further show that germ cells express a novel member of the TGF-{beta} family (Gonadless, Gls) that induces somatic gonad morphogenesis. Loss of Gls resulted in animals lacking somatic gonadal structures but having few, non-proliferative germ cells. We propose a model according to which a small number of primary germ cells drive gonad development though Gls morphogen secretion. The germinal zone in the newly formed gonad, in turn, provides positive feedback to induce secondary germ cells by activating Tfap2 (the master regulator of germ cell fate) in resident pluripotent stem cells. De novo induction of germ cells by gonads in adult life is absent in bilaterians with a sequestered germline. However, the contribution of germ cell signaling to the patterning of somatic gonadal tissue, as observed in Hydractinia, may be a general animal feature.

developmental biology↗

bioRxiv2023

Evolution of apoptotic signalling pathways among metazoans: insights from lophotrochozoans

Apoptosis is the main form of regulated cell death in metazoans. Apoptotic pathways are well characterised in nematode, fly and mammals, leading to a vision of the conservation of apoptotic pathways in metazoans. However, we recently showed that intrinsic apoptosis is in fact divergent among metazoans. In addition, extrinsic apoptosis is poorly studied in non-mammalian animals, making its evolution unclear. Consequently, our understanding of apoptotic signalling pathways evolution is a black-box which must be illuminated by extending research to new biological systems. Lophotrochozoans are a major clade of metazoans which, despite their considerable biological diversity and key phylogenetic position as sister group of ecdysozoans (i.e. fly, nematode), are poorly explored, especially regarding apoptosis mechanisms. Traditionally each apoptotic signalling pathway was considered to rely on a specific initiator Caspase, associated with an activator. To shed light on apoptosis evolution in animals, we explored the evolutionary history of initiator Caspases, Caspase activators and the BCL-2 family (which control mitochondrial apoptotic pathway) in lophotrochozoans using phylogenetic analysis and protein interaction predictions. We discovered a diversification of initiator Caspases in molluscs, annelids and brachiopods, and the loss of key extrinsic apoptosis components in platyhelminths, along with the emergence of a clade specific Caspase with an ankyrin pro-domain. Taken together, our data show a specific history of apoptotic actors evolution in lophotrochozoans, further demonstrating the appearance of distinct apoptotic signalling pathways during metazoan evolution. Significance statementApoptosis, a form of programmed cell death, has been long studied in model organisms such as fly, mouse, and in humans. The restricted focus on these models has led to an overall view that the evolution of genes involved in apoptosis is highly conserved across all animals. The advent of next generation sequencing has led to a boom in the omics data available across the tree of life. Thanks to this, we explored the evolution of key genes involved in apoptosis in the clade Lophotrochozoa (i.e. molluscs, annelids, flatworms, brachiopods), one of the three large clades that make up bilaterian animals. We found a complex evolutionary history of apoptosis genes, with multiple losses, gains, divergences and redundancies, highlighting the value of exploring gene evolution and apoptotic mechanisms in Lophotrochozoans.

evolutionary biology↗

bioRxiv2022

Pluripotent, germ cell competent adult stem cells underlie cnidarian plant-like life history

In most animals, pluripotency is irreversibly lost post-gastrulation. By this stage, all embryonic cells have already committed either to one of the somatic lineages (ectoderm, endoderm, mesoderm) or to the germline. The lack of pluripotent cells in adult life may be linked to organismal aging. Cnidarians (corals, and jellyfish) are an early branch of animals that do not succumb to age, but the developmental potential of their adult stem cells remains unclear. Here, we show that adult stem cells in the cnidarian Hydractinia symbiolongicarpus (known as i-cells) are pluripotent. We transplanted single i-cells from transgenic fluorescent donors to wild type recipients and followed them in vivo in the translucent animals. Single engrafted i-cells self-renewed and contributed to all somatic lineages and to gamete production, co-existing with and eventually displacing the allogeneic recipients cells. Hence, a fully functional, sexually competent individual can originate from a single adult i-cell. Given that some of their cells remain pluripotent beyond embryogenesis and throughout life, we conclude that Hydractinia embryos never complete gastrulation. Pluripotent i-cells underlie a regenerative, plant-like life history in these animals.

developmental biology↗

bioRxiv2022

Senescence-induced cellular reprogramming drives cnidarian whole-body regeneration

Cell fate stability is essential to maintaining law and order in complex animals. However, high stability comes at the cost of reduced plasticity and, by extension, poor regenerative ability. This evolutionary trade-off has resulted in most modern animals being rather simple and regenerative or complex and non-regenerative. The mechanisms mediating cellular plasticity and allowing for regeneration remain unknown. We show that signals emitted by senescent cells can destabilize the differentiated state of neighboring somatic cells, reprogramming them into stem cells that are capable of driving whole-body regeneration in the cnidarian Hydractinia symbiolongicarpus. Pharmacological or genetic inhibition of senescence prevented reprogramming and regeneration. Conversely, induction of transient ectopic senescence in a regenerative context resulted in supernumerary stem cells and faster regeneration. We propose that senescence signaling is an ancient mechanism mediating cellular plasticity. Understanding the senescence environment that promotes cellular reprogramming could provide a new avenue to enhance regeneration.

developmental biology↗

bioRxiv2021

Intrinsic apoptosis is evolutionary divergent among metazoans

Apoptosis is regulated cell death that depends on caspases. Upstream of each apoptotic signalling pathway is involved a specific initiator caspase. Characterised in nematode, fly and mammals, intrinsic apoptosis is considered to be ancestral and conserved among animals, and depends on shared initiators; caspase-9, Apaf-1 and Bcl-2. However, the biochemical role of mitochondria, the pivotal function of cytochrome c and the modality of caspase activation remain highly heterogeneous and hide profound molecular divergences among apoptotic pathways in animals. Uncovering the phylogenetic history of apoptotic actors, especially caspases, is crucial to shed light on intrinsic apoptosis evolutionary history. Here, we demonstrate by phylogenetic analyses, that caspase-9, the fundamental key of intrinsic apoptosis, is deuterostome-specific, while caspase-2 is ancestral to bilaterians. Our analysis of Bcl-2 and Apaf-1 confirm heterogeneity in functional organisation of apoptotic pathways in animals. Our results support emergence of distinct intrinsic apoptotic pathways during metazoan evolution.

evolutionary biology↗