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J. Dev. Biol., Volume 6, Issue 1 (March 2018)

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Research

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Open AccessArticle Imaging Neuronal Activity in the Optic Tectum of Late Stage Larval Zebrafish
J. Dev. Biol. 2018, 6(1), 6; doi:10.3390/jdb6010006
Received: 6 February 2018 / Revised: 1 March 2018 / Accepted: 6 March 2018 / Published: 9 March 2018
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Abstract
The zebrafish is an established model to study the development and function of visual neuronal circuits in vivo, largely due to their optical accessibility at embryonic and larval stages. In the past decade multiple experimental paradigms have been developed to study visually-driven behaviours,
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The zebrafish is an established model to study the development and function of visual neuronal circuits in vivo, largely due to their optical accessibility at embryonic and larval stages. In the past decade multiple experimental paradigms have been developed to study visually-driven behaviours, particularly those regulated by the optic tectum, the main visual centre in lower vertebrates. With few exceptions these techniques are limited to young larvae (7–9 days post-fertilisation, dpf). However, many forms of visually-driven behaviour, such as shoaling, emerge at later developmental stages. Consequently, there is a need for an experimental paradigm to image the visual system in zebrafish larvae beyond 9 dpf. Here, we show that using NBT:GCaMP3 line allows for imaging neuronal activity in the optic tectum in late stage larvae until at least 21 dpf. Utilising this line, we have characterised the receptive field properties of tectal neurons of the 2–3 weeks old fish in the cell bodies and the neuropil. The NBT:GCaMP3 line provides a complementary approach and additional opportunities to study neuronal activity in late stage zebrafish larvae. Full article
(This article belongs to the Special Issue Zebrafish - A Model System for Developmental Biology Study)
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Open AccessArticle Ethanol Exposure Causes Muscle Degeneration in Zebrafish
J. Dev. Biol. 2018, 6(1), 7; doi:10.3390/jdb6010007
Received: 12 January 2018 / Revised: 5 March 2018 / Accepted: 8 March 2018 / Published: 9 March 2018
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Abstract
Alcoholic myopathies are characterized by neuromusculoskeletal symptoms such as compromised movement and weakness. Although these symptoms have been attributed to neurological damage, EtOH may also target skeletal muscle. EtOH exposure during zebrafish primary muscle development or adulthood results in smaller muscle fibers. However,
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Alcoholic myopathies are characterized by neuromusculoskeletal symptoms such as compromised movement and weakness. Although these symptoms have been attributed to neurological damage, EtOH may also target skeletal muscle. EtOH exposure during zebrafish primary muscle development or adulthood results in smaller muscle fibers. However, the effects of EtOH exposure on skeletal muscle during the growth period that follows primary muscle development are not well understood. We determined the effects of EtOH exposure on muscle during this phase of development. Strikingly, muscle fibers at this stage are acutely sensitive to EtOH treatment: EtOH induces muscle degeneration. The severity of EtOH-induced muscle damage varies but muscle becomes more refractory to EtOH as muscle develops. NF-kB induction in muscle indicates that EtOH triggers a pro-inflammatory response. EtOH-induced muscle damage is p53-independent. Uptake of Evans blue dye shows that EtOH treatment causes sarcolemmal instability before muscle fiber detachment. Dystrophin-null sapje mutant zebrafish also exhibit sarcolemmal instability. We tested whether Trichostatin A (TSA), which reduces muscle degeneration in sapje mutants, would affect EtOH-treated zebrafish. We found that TSA and EtOH are a lethal combination. EtOH does, however, exacerbate muscle degeneration in sapje mutants. EtOH also disrupts adhesion of muscle fibers to their extracellular matrix at the myotendinous junction: some detached muscle fibers retain beta-Dystroglycan indicating failure of muscle end attachments. Overexpression of Paxillin, which reduces muscle degeneration in zebrafish deficient for beta-Dystroglycan, is not sufficient to rescue degeneration. Taken together, our results suggest that EtOH exposure has pleiotropic deleterious effects on skeletal muscle. Full article
(This article belongs to the Special Issue Zebrafish - A Model System for Developmental Biology Study)
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Review

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Open AccessReview The Biology of SUMO-Targeted Ubiquitin Ligases in Drosophila Development, Immunity, and Cancer
J. Dev. Biol. 2018, 6(1), 2; doi:10.3390/jdb6010002
Received: 28 November 2017 / Revised: 27 December 2017 / Accepted: 27 December 2017 / Published: 1 January 2018
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Abstract
The ubiquitin and SUMO (small ubiquitin-like modifier) pathways modify proteins that in turn regulate diverse cellular processes, embryonic development, and adult tissue physiology. These pathways were originally discovered biochemically in vitro, leading to a long-standing challenge of elucidating both the molecular cross-talk between
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The ubiquitin and SUMO (small ubiquitin-like modifier) pathways modify proteins that in turn regulate diverse cellular processes, embryonic development, and adult tissue physiology. These pathways were originally discovered biochemically in vitro, leading to a long-standing challenge of elucidating both the molecular cross-talk between these pathways and their biological importance. Recent discoveries in Drosophila established that ubiquitin and SUMO pathways are interconnected via evolutionally conserved SUMO-targeted ubiquitin ligase (STUbL) proteins. STUbL are RING ubiquitin ligases that recognize SUMOylated substrates and catalyze their ubiquitination, and include Degringolade (Dgrn) in Drosophila and RNF4 and RNF111 in humans. STUbL are essential for early development of both the fly and mouse embryos. In the fly embryo, Dgrn regulates early cell cycle progression, sex determination, zygotic gene transcription, segmentation, and neurogenesis, among other processes. In the fly adult, Dgrn is required for systemic immune response to pathogens and intestinal stem cell regeneration upon infection. These functions of Dgrn are highly conserved in humans, where RNF4-dependent ubiquitination potentiates key oncoproteins, thereby accelerating tumorigenesis. Here, we review the lessons learned to date in Drosophila and highlight their relevance to cancer biology. Full article
(This article belongs to the Special Issue Drosophila - A Model System for Developmental Biology)
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Open AccessReview Taking the Occam’s Razor Approach to Hedgehog Lipidation and Its Role in Development
J. Dev. Biol. 2018, 6(1), 3; doi:10.3390/jdb6010003
Received: 5 January 2018 / Revised: 24 January 2018 / Accepted: 25 January 2018 / Published: 30 January 2018
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Abstract
All Hedgehog (Hh) proteins signal from producing cells to distant receiving cells despite being synthesized as N-and C-terminally lipidated, membrane-tethered molecules. To explain this paradoxical situation, over the past 15 years, several hypotheses have been postulated that tie directly into this property, such
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All Hedgehog (Hh) proteins signal from producing cells to distant receiving cells despite being synthesized as N-and C-terminally lipidated, membrane-tethered molecules. To explain this paradoxical situation, over the past 15 years, several hypotheses have been postulated that tie directly into this property, such as Hh transport on cellular extensions called cytonemes or on secreted vesicles called lipophorins and exosomes. The alternative situation that tight membrane association merely serves to prevent unregulated Hh solubilization has been addressed by biochemical and structural studies suggesting Hh extraction from the membrane or proteolytic Hh release. While some of these models may act in different organisms, tissues or developmental programs, others may act together to specify Hh short- and long-range signaling in the same tissues. To test and rank these possibilities, we here review major models of Hh release and transport and hypothesize that the (bio)chemical and physical properties of firmly established, homologous, and functionally essential biochemical Hh modifications are adapted to specify and determine interdependent steps of Hh release, transport and signaling, while ruling out other steps. This is also described by the term “congruence”, meaning that the logical combination of biochemical Hh modifications can reveal their true functional implications. This combined approach reveals potential links between models of Hh release and transport that were previously regarded as unrelated, thereby expanding our view of how Hhs can steer development in a simple, yet extremely versatile, manner. Full article
(This article belongs to the collection Hedgehog Signaling in Embryogenesis)
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Open AccessReview Dynamic Tissue Rearrangements during Vertebrate Eye Morphogenesis: Insights from Fish Models
J. Dev. Biol. 2018, 6(1), 4; doi:10.3390/jdb6010004
Received: 1 February 2018 / Revised: 22 February 2018 / Accepted: 27 February 2018 / Published: 28 February 2018
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Abstract
Over the last thirty years, fish models, such as the zebrafish and medaka, have become essential to pursue developmental studies and model human disease. Community efforts have led to the generation of wide collections of mutants, a complete sequence of their genomes, and
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Over the last thirty years, fish models, such as the zebrafish and medaka, have become essential to pursue developmental studies and model human disease. Community efforts have led to the generation of wide collections of mutants, a complete sequence of their genomes, and the development of sophisticated genetic tools, enabling the manipulation of gene activity and labelling and tracking of specific groups of cells during embryonic development. When combined with the accessibility and optical clarity of fish embryos, these approaches have made of them an unbeatable model to monitor developmental processes in vivo and in real time. Over the last few years, live-imaging studies in fish have provided fascinating insights into tissue morphogenesis and organogenesis. This review will illustrate the advantages of fish models to pursue morphogenetic studies by highlighting the findings that, in the last decade, have transformed our understanding of eye morphogenesis. Full article
(This article belongs to the Special Issue Zebrafish - A Model System for Developmental Biology Study)
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Open AccessReview Flying the RNA Nest: Drosophila Reveals Novel Insights into the Transcriptome Dynamics of Early Development
J. Dev. Biol. 2018, 6(1), 5; doi:10.3390/jdb6010005
Received: 15 February 2018 / Revised: 1 March 2018 / Accepted: 5 March 2018 / Published: 7 March 2018
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Abstract
Early development is punctuated by a series of pervasive and fast paced transitions. These events reshape a differentiated oocyte into a totipotent embryo and allow it to gradually mount a genetic program of its own, thereby framing a new organism. Specifically, developmental transitions
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Early development is punctuated by a series of pervasive and fast paced transitions. These events reshape a differentiated oocyte into a totipotent embryo and allow it to gradually mount a genetic program of its own, thereby framing a new organism. Specifically, developmental transitions that ensure the maternal to embryonic control of developmental events entail a deep remodeling of transcriptional and transcriptomic landscapes. Drosophila provides an elegant and genetically tractable system to investigate these conserved changes at a dazzling developmental pace. Here, we review recent studies applying emerging technologies such as ribosome profiling, in situ Hi-C chromatin probing and live embryo RNA imaging to investigate the transcriptional dynamics at play during Drosophila embryogenesis. In light of this new literature, we revisit the main models of zygotic genome activation (ZGA). We also review the contributions played by zygotic transcription in shaping embryogenesis and explore emerging concepts of processes such as transcriptional bursting and transcriptional memory. Full article
(This article belongs to the Special Issue Drosophila - A Model System for Developmental Biology)
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Other

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Open AccessFeature PaperCommentary Modeling Alzheimer’s and Other Age Related Human Diseases in Embryonic Systems
J. Dev. Biol. 2018, 6(1), 1; doi:10.3390/jdb6010001
Received: 22 November 2017 / Revised: 19 December 2017 / Accepted: 21 December 2017 / Published: 22 December 2017
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Abstract
Modeling human disease in animals is an important strategy to discover potential methods of intervention. We suggest that there is much to be gained by employing a multi-model approach that takes advantage of different animal systems used in the laboratory simultaneously. We use
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Modeling human disease in animals is an important strategy to discover potential methods of intervention. We suggest that there is much to be gained by employing a multi-model approach that takes advantage of different animal systems used in the laboratory simultaneously. We use the example of modeling Alzheimer’s disease in Drosophila melanogaster, Caenorhabditis elegans, and Danio rerio to illustrate how such an approach can be employed to investigate the pathophysiology of the disease. Full article
(This article belongs to the Special Issue Drosophila - A Model System for Developmental Biology)
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