Biologist interested in Stem Cell Biology and Regenerative Medicine. Currently, I am a doctoral student at the National University of Ireland Galway focusing on the role of SoxB family of transcription factors during nervous system development and regeneration using the animal model Hydractinia; a well-established stem cell animal model. Ι received my BSc with Honors from Lancaster University, UK where Ι completed my Master’s degree in Tissue Engineering as well. After finishing my studies, I worked for the Cancer Research UK, University of Southampton on Chronic Lymphocytic Leukemia. I can be contacted at firstname.lastname@example.org or email@example.com.
Why is good to know how the nervous system develops and regenerates ?
The structure and function of the nervous system remains one of the most fascinating and yet challenging aspects in biology. The way in which neural progenitors (NPs) are specified and spatially arranged, and how they proliferate, differentiate and migrate to form a functional nervous system is controlled by patterning mechanisms which are not fully understood. When it comes to neuronal regeneration, the picture is even more blurry.
Unraveling how these patterning mechanisms are controlled and regulated to form a neuronal network during tissue homeostasis and regeneration is a complicated task for every animal model. To address this issue, we use Hydractinia, a marine cnidarian hydrozoid which encompasses remarkable abilities to regenerate any lost body parts, including functional nervous system after injury.
The origin of committed nerve cells in the regenerating tissues and the molecular mechanisms driving their patterning is not known. To explore this subject, we generated transgenic reporter animals expressing fluorescent proteins under the control of different nerve-cell related genes, including three SoxB genes. Lineage tracing of differentiated neurons, as well as SoxB+ cells, that are expressed at different stages of neural fate establishment, will clarify the role of each cell type and will help to understand how the neuronal network is established both in development and in head regeneration.
Abstract: The foundation of the diverse metazoan nervous systems is laid by embryonic patterning mechanisms, involving the generation and movement of neural progenitors and their progeny. Here we divide early neurogenesis into discrete elements, including origin, pattern, proliferation, and movement of neuronal progenitors, which are controlled by conserved gene cassettes. We review these neurogenetic mechanisms in representatives of the different metazoan clades, with the goal to build a conceptual framework in which one can ask specific questions, such as which of these mechanisms potentially formed part of the developmental "toolkit" of the bilaterian ancestor and which evolved later.
Pub.: 25 Feb '15, Pinned: 30 Aug '17
Abstract: Sox family transcription factors are well-established regulators of cell fate decisions during development. Accumulating evidence documents that they play additional roles in adult tissue homeostasis and regeneration. Remarkably, forced expression of Sox factors, in combination with other synergistic factors, reprograms differentiated cells into somatic or pluripotent stem cells. Dysregulation of Sox factors has been further implicated in diseases including cancer. Here, we review molecular and functional evidence linking Sox proteins with stem cell biology, cellular reprogramming, and disease with an emphasis on Sox2.
Pub.: 08 Jan '13, Pinned: 30 Aug '17
Abstract: The function of Notch signaling was previously studied in two cnidarians, Hydra and Nematostella, representing the lineages Hydrozoa and Anthozoa, respectively. Using pharmacological inhibition in Hydra and a combination of pharmacological and genetic approaches in Nematostella, it was shown in both animals that Notch is required for tentacle morphogenesis and for late stages of stinging cell maturation. Surprisingly, a role for Notch in neural development, which is well documented in bilaterians, was evident in embryonic Nematostella but not in adult Hydra. Adult neurogenesis in the latter seemed to be unaffected by DAPT, a drug that inhibits Notch signaling. To address this apparent discrepancy we studied the role of Notch in Hydractinia echinata, an additional hydrozoan, in all life stages. Using CRISPR-Cas9 mediated mutagenesis, transgenesis, and pharmacological interference we show that Notch is dispensable for Hydractinia normal neurogenesis in all life stages but is required for the maturation of stinging cells and for tentacle morphogenesis. Our results are consistent with a conserved role for Notch in morphogenesis and nematogenesis across Cnidaria, and a lineage specific loss of Notch dependence in neurogenesis in hydrozoans.
Pub.: 12 Jun '17, Pinned: 30 Aug '17
Abstract: SoxB transcription factors and histone deacetylases (HDACs) are each major players in the regulation of neurogenesis, but a functional link between them has not been previously demonstrated. Here, we show that SoxB2 and Hdac2 act together to regulate neurogenesis in the cnidarian Hydractinia echinata during tissue homeostasis and head regeneration. We find that misexpression of SoxB genes modifies the number of neural cells in all life stages and interferes with head regeneration. Hdac2 was co-expressed with SoxB2, and its downregulation phenocopied SoxB2 knockdown. We also show that SoxB2 and Hdac2 promote each other's transcript levels, but Hdac2 counteracts this amplification cycle by deacetylating and destabilizing SoxB2 protein. Finally, we present evidence for conservation of these interactions in human neural progenitors. We hypothesize that crosstalk between SoxB transcription factors and Hdac2 is an ancient feature of metazoan neurogenesis and functions to stabilize the correct levels of these multifunctional proteins.
Pub.: 09 Feb '17, Pinned: 30 Aug '17
Abstract: Cnidarians possess remarkable powers of regeneration, but the cellular and molecular mechanisms underlying this capability are unclear. Studying the hydrozoan Hydractinia echinata we show that a burst of stem cell proliferation occurs following decapitation, forming a blastema at the oral pole within 24 hr. This process is necessary for head regeneration. Knocking down Piwi1, Vasa, Pl10 or Ncol1 expressed by blastema cells inhibited regeneration but not blastema formation. EdU pulse-chase experiments and in vivo tracking of individual transgenic Piwi1(+) stem cells showed that the cellular source for blastema formation is migration of stem cells from a remote area. Surprisingly, no blastema developed at the aboral pole after stolon removal. Instead, polyps transformed into stolons and then budded polyps. Hence, distinct mechanisms act to regenerate different body parts in Hydractinia. This model, where stem cell behavior can be monitored in vivo at single cell resolution, offers new insights for regenerative biology.
Pub.: 18 Apr '15, Pinned: 30 Aug '17
Abstract: Hydractinia species have been animal models in developmental biology and comparative immunology for over a century, but are having a renaissance due to the establishment of modern genetic and genomic tools by the growing community of researchers utilizing them. Hydractinia has a predictable and accessible life cycle and its stem cell system, known as interstitial- or i-cells has been a paradigm for animal stem cells since the late 1800s. In adult Hydractinia, i-cells continuously provide progenitors to sustain clonal growth, tissue homeostasis, sexual reproduction and regeneration. We review recent developments in stem cell and regeneration research centered on this animal. Hydractinia joins an established team of cnidarian genetic models in times of rapid progress in these disciplines. While each animal is particularly suited to specific experimental settings, jointly they can provide an integrative insight into the diversity of animal stem cell systems, how they drive regeneration, and how they evolved.
Pub.: 06 Jul '16, Pinned: 30 Aug '17
Abstract: With the rapid increase of the quantity of molecular data, many animals joined the ranks of the so-called 'emerging models' of Evo-Devo. One of the necessary steps in converting an emerging model into an established one is gaining comprehensive knowledge of its normal embryonic development. The marine colonial hydrozoan Hydractinia echinata - an excellent model for research on stem cells, metamorphosis, and allorecognition - has been studied for decades. Yet knowledge of its embryonic development remains fragmentary and incomplete. Here we provide a detailed account of H. echinata embryonic development using in vivo observations, histology, immunohistochemistry, and electron microscopy. Furthermore, we propose a model describing the cellular basis of the morphogenetic movements occurring during development and also reveal a functional link between canonical Wnt signaling and regional differences in the morphology of the embryo. Hydractinia embryogenesis is an example of the diversity and plasticity of hydrozoan development where multiple routes lead to the same result - the formation of a normal planula larva.
Pub.: 28 Oct '14, Pinned: 30 Aug '17
Abstract: Adult neural stem and progenitor cells (NSPCs) offer a unique opportunity for neural regeneration and niche modification in physiopathological conditions, harnessing the capability to modify from neuronal circuits to glial scar. Findings exposing the vast plasticity and potential of NSPCs have accumulated over the past years and we currently know that adult NSPCs can naturally give rise not only to neurons but also to astrocytes and reactive astrocytes, and eventually to oligodendrocytes through genetic manipulation. We can consider NSPCs as endogenous flexible tools to fight against neurodegenerative and neurological disorders and aging. In addition, NSPCs can be considered as active agents contributing to chronic brain alterations and as relevant cell populations to be preserved, so that their main function, neurogenesis, is not lost in damage or disease. Altogether we believe that learning to manipulate NSPC is essential to prevent, ameliorate or restore some of the cognitive deficits associated with brain disease and injury, and therefore should be considered as target for future therapeutic strategies. The first step to accomplish this goal is to target them specifically, by unveiling and understanding their unique markers and signaling pathways.
Pub.: 29 Jul '17, Pinned: 30 Aug '17
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