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Lebedeva, T.

Publications and source records attributed to Lebedeva, T..

5 recordsLinked to original sources

The ancient metazoan cytoplasmic intermediate filament protein, Cilin, shapes cilia arrangement and tissue architecture

The emergence of animal multicellularity demanded novel cytoskeletal systems to support cellular architecture and tissue integrity. Cytoplasmic intermediate filaments (cIFs) are essential components of this scaffold, yet their evolutionary origins remain obscure. Here, we identify and characterize a lamin-derived, bona fide cIF protein in a ctenophore--a sister lineage to all other extant animals. We name this protein Cilin. Unlike nuclear lamins, Cilin lacks a nuclear localization signal and instead localizes predominantly to motile ciliary structures, including comb plates, the aboral organ, and sperm flagella, indicating a central role in ciliary architecture and function. Remarkably, Cilin is also present in non-ciliated cells, suggesting early functional diversification of cIFs in animal evolution. Phylogenetic and structural analyses position Cilin within an ancestral class of intermediate filament proteins, homologous to cnidarian and bilaterian nematocilins and lamin-tail-domain-containing (LMNTD) proteins. In humans, LMNTD proteins are enriched in ciliated epithelia and spermatids, pointing to a deeply conserved role in cilia-associated functions. These findings establish cilins as the earliest lamin-derived cytoplasmic intermediate filament proteins in metazoans, likely contributing to both ciliary function and the emergence of multicellular tissue organization.

cell biology↗

Notch, beta-catenin and MAPK signaling segregate endoderm and mesoderm in the diploblast Nematostella vectensis

Cnidaria are typically considered diploblastic (i.e. consisting of two germ layers) in contrast to their triploblastic sister clade, the Bilateria. However, a recent study suggested that sea anemones and other cnidarians have three segregated germ layer identities, corresponding to the bilaterian germ layers1. Here, we investigated, how the three germ layer identities are specified during early development of the sea anemone Nematostella vectensis. First, the mesodermal territory is specified at the animal pole at 6 hours postfertilization, followed by the specification of a ring of endodermal territory between mesoderm and ectoderm. We then assessed the role of {beta}-catenin, MAPK and Notch signaling pathways during mesoderm and endoderm formation. Our results show that the mesoderm is initiated by MAPK signaling and simultaneously restricted to the future oral side by mutually exclusive nuclear {beta}-catenin signaling. The mesodermal cells then express the Delta ligand, while the ectodermal cells express the Notch receptor. Inhibition of Notch signaling as well as ectopic expression of the Notch intracellular domain showed that endodermal tissue identity is induced by Notch signaling at the boundary between mesoderm and ectoderm. We propose a new model that outlines the different steps leading to the segregation of mesoderm and endoderm identities in Nematostella, confirming the presence of 3 distinct germ layer identities in this cnidarian. Notably, the observed crosstalk of MAPK, {beta}-catenin and Notch signaling in the specification of three germ layers in Nematostella is highly reminiscent to early stage gastrulae of sea urchins suggesting that triploblasty may predate the split of cnidarians and bilaterians.

developmental biology↗

β-catenin-dependent endomesoderm specification appears to be a Bilateria-specific co-option

Endomesoderm specification based on a maternal {beta}-catenin signal and axial patterning by interpreting a gradient of zygotic Wnt/{beta}-catenin signalling was suggested to predate the split between Bilateria and their evolutionary sister Cnidaria. However, in Cnidaria, the roles of {beta}-catenin signalling in both these processes have not been proven directly. Here, by tagging the endogenous {beta}-catenin protein in the sea anemone Nematostella vectensis, we show that the oral-aboral axis in a cnidarian is indeed patterned by a gradient of {beta}-catenin signalling. Unexpectedly, in a striking contrast to Bilateria, Nematostella endoderm specification takes place opposite to the part of the embryo, where {beta}-catenin is translocated into the nuclei. This suggests that {beta}-catenin-dependent endomesoderm specification is a Bilateria-specific co-option, which may have linked endomesoderm specification with the subsequent posterior-anterior patterning.

developmental biology↗

Single cell transcriptomics identifies conserved regulators of neurosecretory lineages

Communication in bilaterian nervous systems is mediated by electrical and secreted signals, however, the evolutionary origin and relation of neurons to other secretory cell types has not been elucidated. Here we use developmental single cell RNA-sequencing in the cnidarian Nematostella vectensis, representing an early evolutionary lineage with a simple nervous system. Validated by transgenics, we demonstrate that neurons, stinging cells, and gland cells arise from a common multipotent progenitor population. We identify the conserved transcription factor gene SoxC as a key upstream regulator of all neurosecretory lineages and demonstrate that SoxC knockdown eliminates both neuronal and secretory cell types. While in vertebrates and many other bilaterians neurogenesis is largely restricted to early developmental stages, we show that in the sea anemone differentiation of neurosecretory cells is maintained throughout all life stages, and follows the same molecular trajectories from embryo to adulthood, ensuring lifelong homeostasis of neurosecretory cell lineages.

developmental biology↗

Sea anemone Frizzled receptors play partially redundant roles in the oral-aboral axis patterning

Canonical Wnt (cWnt) signaling is involved in a plethora of basic developmental processes such as endomesoderm specification, gastrulation and patterning the main body axis. To activate the signal, Wnt ligands form complexes with LRP5/6 and Frizzled receptors, which leads to nuclear translocation of {beta}-catenin and transcriptional response. In Bilateria, the expression of different Frizzled genes is often partially overlapping, and their functions are known to be redundant in several developmental contexts. Here we demonstrate that all four Frizzled receptors take part in the cWnt-mediated oral-aboral axis patterning in the cnidarian Nematostella vectensis but show partially redundant functions. However, we do not see evidence for their involvement in the specification of the endoderm - an earlier event likely relying on maternal, intracellular {beta}-catenin signaling components. Finally, we demonstrate that the main Wnt ligands crucial for the early oral-aboral patterning are Wnt3 and Wnt4. Comparison of our data to the knowledge from other models suggests that distinct but overlapping expression domains and partial functional redundancy of cnidarian and bilaterian Frizzled genes may represent a shared ancestral trait.

developmental biology↗