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  This is an Open Access Journal Open Access journal
   ISSN (Online) 2221-3759
   Published by MDPI Homepage  [202 journals]
  • JDB, Vol. 6, Pages 8: Wingless/Wnt Signaling in Intestinal Development,
           Homeostasis, Regeneration and Tumorigenesis: A Drosophila Perspective

    • Authors: Ai Tian, Hassina Benchabane, Yashi Ahmed
      First page: 8
      Abstract: In mammals, the Wnt/β-catenin signal transduction pathway regulates intestinal stem cell maintenance and proliferation, whereas Wnt pathway hyperactivation, resulting primarily from the inactivation of the tumor suppressor Adenomatous polyposis coli (APC), triggers the development of the vast majority of colorectal cancers. The Drosophila adult gut has recently emerged as a powerful model to elucidate the mechanisms by which Wingless/Wnt signaling regulates intestinal development, homeostasis, regeneration, and tumorigenesis. Herein, we review recent insights on the roles of Wnt signaling in Drosophila intestinal physiology and pathology.
      Citation: Journal of Developmental Biology
      PubDate: 2018-03-28
      DOI: 10.3390/jdb6020008
      Issue No: Vol. 6, No. 2 (2018)
  • JDB, Vol. 6, Pages 9: Requirement of the Dynein-Adaptor Spindly for
           Mitotic and Post-Mitotic Functions in Drosophila

    • Authors: Giuliana Clemente, Matthew Hannaford, Hamze Beati, Katja Kapp, Jens Januschke, Eric Griffis, Hans-Arno Müller
      First page: 9
      Abstract: Spindly was originally identified as a specific regulator of Dynein activity at the kinetochore. In early prometaphase, Spindly recruits the Dynein/Dynactin complex, promoting the establishment of stable kinetochore-microtubule interactions and progression into anaphase. While details of Spindly function in mitosis have been worked out in cultured human cells and in the C. elegans zygote, the function of Spindly within the context of an organism has not yet been addressed. Here, we present loss- and gain-of-function studies of Spindly using transgenic RNAi in Drosophila. Knock-down of Spindly in the female germ line results in mitotic arrest during embryonic cleavage divisions. We investigated the requirements of Spindly protein domains for its localisation and function, and found that the carboxy-terminal region controls Spindly localisation in a cell-type specific manner. Overexpression of Spindly in the female germ line is embryonic lethal and results in altered egg morphology. To determine whether Spindly plays a role in post-mitotic cells, we altered Spindly protein levels in migrating cells and found that ovarian border cell migration is sensitive to the levels of Spindly protein. Our study uncovers novel functions of Spindly and a differential, functional requirement for its carboxy-terminal region in Drosophila.
      Citation: Journal of Developmental Biology
      PubDate: 2018-03-30
      DOI: 10.3390/jdb6020009
      Issue No: Vol. 6, No. 2 (2018)
  • JDB, Vol. 6, Pages 2: The Biology of SUMO-Targeted Ubiquitin Ligases in
           Drosophila Development, Immunity, and Cancer

    • Authors: Mona Abed, Eliya Bitman-Lotan, Amir Orian
      First page: 2
      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 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.
      Citation: Journal of Developmental Biology
      PubDate: 2018-01-01
      DOI: 10.3390/jdb6010002
      Issue No: Vol. 6, No. 1 (2018)
  • JDB, Vol. 6, Pages 3: Taking the Occam’s Razor Approach to Hedgehog
           Lipidation and Its Role in Development

    • Authors: Dominique Manikowski, Philipp Kastl, Kay Grobe
      First page: 3
      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 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.
      Citation: Journal of Developmental Biology
      PubDate: 2018-01-30
      DOI: 10.3390/jdb6010003
      Issue No: Vol. 6, No. 1 (2018)
  • JDB, Vol. 6, Pages 4: Dynamic Tissue Rearrangements during Vertebrate Eye
           Morphogenesis: Insights from Fish Models

    • Authors: Florencia Cavodeassi
      First page: 4
      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 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.
      Citation: Journal of Developmental Biology
      PubDate: 2018-02-28
      DOI: 10.3390/jdb6010004
      Issue No: Vol. 6, No. 1 (2018)
  • JDB, Vol. 6, Pages 5: Flying the RNA Nest: Drosophila Reveals Novel
           Insights into the Transcriptome Dynamics of Early Development

    • Authors: Fabio Lefebvre, Éric Lécuyer
      First page: 5
      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 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.
      Citation: Journal of Developmental Biology
      PubDate: 2018-03-07
      DOI: 10.3390/jdb6010005
      Issue No: Vol. 6, No. 1 (2018)
  • JDB, Vol. 6, Pages 6: Imaging Neuronal Activity in the Optic Tectum of
           Late Stage Larval Zebrafish

    • Authors: Katharina Bergmann, Paola Meza Santoscoy, Konstantinos Lygdas, Yulia Nikolaeva, Ryan MacDonald, Vincent Cunliffe, Anton Nikolaev
      First page: 6
      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, 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.
      Citation: Journal of Developmental Biology
      PubDate: 2018-03-09
      DOI: 10.3390/jdb6010006
      Issue No: Vol. 6, No. 1 (2018)
  • JDB, Vol. 6, Pages 7: Ethanol Exposure Causes Muscle Degeneration in

    • Authors: Elizabeth Coffey, Maggie Pasquarella, Michelle Goody, Clarissa Henry
      First page: 7
      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, 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.
      Citation: Journal of Developmental Biology
      PubDate: 2018-03-09
      DOI: 10.3390/jdb6010007
      Issue No: Vol. 6, No. 1 (2018)
  • JDB, Vol. 6, Pages 1: Modeling Alzheimer’s and Other Age Related Human
           Diseases in Embryonic Systems

    • Authors: Chu Lim, Ajay Mathuru
      First page: 1
      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 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.
      Citation: Journal of Developmental Biology
      PubDate: 2017-12-22
      DOI: 10.3390/jdb6010001
      Issue No: Vol. 6, No. 1 (2017)
  • JDB, Vol. 5, Pages 10: The Roles of the Wnt-Antagonists Axin and Lrp4
           during Embryogenesis of the Red Flour Beetle Tribolium castaneum

    • Authors: Romy Prühs, Anke Beermann, Reinhard Schröder
      First page: 10
      Abstract: In both vertebrates and invertebrates, the Wnt-signaling pathway is essential for numerous processes in embryogenesis and during adult life. Wnt activity is fine-tuned at various levels by the interplay of a number of Wnt-agonists (Wnt ligands, Frizzled-receptors, Lrp5/6 coreceptors) and Wnt-antagonists (among them Axin, Secreted frizzled and Lrp4) to define anterior–posterior polarity of the early embryo and specify cell fate in organogenesis. So far, the functional analysis of Wnt-pathway components in insects has concentrated on the roles of Wnt-agonists and on the Wnt-antagonist Axin. We depict here additional features of the Wnt-antagonist Axin in the flour beetle Tribolium castaneum. We show that Tc-axin is dynamically expressed throughout embryogenesis and confirm its essential role in head development. In addition, we describe an as yet undetected, more extreme Tc-axin RNAi-phenotype, the ectopic formation of posterior abdominal segments in reverse polarity and a second hindgut at the anterior. For the first time, we describe here that an lrp4 ortholog is involved in axis formation in an insect. The Tribolium Lrp4 ortholog is ubiquitously expressed throughout embryogenesis. Its downregulation via maternal RNAi results in the reduction of head structures but not in axis polarity reversal. Furthermore, segmentation is impaired and larvae develop with a severe gap-phenotype. We conclude that, as in vertebrates, Tc-lrp4 functions as a Wnt-inhibitor in Tribolium during various stages of embryogenesis. We discuss the role of both components as negative modulators of Wnt signaling in respect to axis formation and segmentation in Tribolium.
      Citation: Journal of Developmental Biology
      PubDate: 2017-10-15
      DOI: 10.3390/jdb5040010
      Issue No: Vol. 5, No. 4 (2017)
  • JDB, Vol. 5, Pages 11: Contributions of Noncanonical Smoothened Signaling
           During Embryonic Development

    • Authors: Tanushree Pandit, Stacey Ogden
      First page: 11
      Abstract: The Sonic Hedgehog (Shh) signaling pathway is active during embryonic development in metazoans, and provides instructional cues necessary for proper tissue patterning. The pathway signal transducing component, Smoothened (Smo), is a G protein-coupled receptor (GPCR) that has been demonstrated to signal through at least two effector routes. The first is a G protein–independent canonical route that signals to Gli transcriptional effectors to establish transcriptional programs specifying cell fate during early embryonic development. The second, commonly referred to as the noncanonical Smo signal, induces rapid, transcription-independent responses that are essential for establishing and maintaining distinct cell behaviors during development. Herein, we discuss contributions of this noncanonical route during embryonic development. We also highlight important open questions regarding noncanonical Smo signal route selection during development, and consider implications of noncanonical signal corruption in disease.
      Citation: Journal of Developmental Biology
      PubDate: 2017-10-17
      DOI: 10.3390/jdb5040011
      Issue No: Vol. 5, No. 4 (2017)
  • JDB, Vol. 5, Pages 12: Roles of the Hedgehog Signaling Pathway in
           Epidermal and Hair Follicle Development, Homeostasis, and Cancer

    • Authors: Yoshinori Abe, Nobuyuki Tanaka
      First page: 12
      Abstract: The epidermis is the outermost layer of the skin and provides a protective barrier against environmental insults. It is a rapidly-renewing tissue undergoing constant regeneration, maintained by several types of stem cells. The Hedgehog (HH) signaling pathway is one of the fundamental signaling pathways that contributes to epidermal development, homeostasis, and repair, as well as to hair follicle development and follicle bulge stem cell maintenance. The HH pathway interacts with other signal transduction pathways, including those activated by Wnt, bone morphogenetic protein, platelet-derived growth factor, Notch, and ectodysplasin. Furthermore, aberrant activation of HH signaling is associated with various tumors, including basal cell carcinoma. Therefore, an understanding of the regulatory mechanisms of the HH signaling pathway is important for elucidating fundamental mechanisms underlying both organogenesis and carcinogenesis. In this review, we discuss the role of the HH signaling pathway in the development and homeostasis epidermis and hair follicles, and in basal cell carcinoma formation, providing an update of current knowledge in this field.
      Citation: Journal of Developmental Biology
      PubDate: 2017-11-20
      DOI: 10.3390/jdb5040012
      Issue No: Vol. 5, No. 4 (2017)
  • JDB, Vol. 5, Pages 13: Emerging Roles of DYRK Kinases in Embryogenesis and
           Hedgehog Pathway Control

    • Authors: Rajeev Singh, Matthias Lauth
      First page: 13
      Abstract: Hedgehog (Hh)/GLI signaling is an important instructive cue in various processes during embryonic development, such as tissue patterning, stem cell maintenance, and cell differentiation. It also plays crucial roles in the development of many pediatric and adult malignancies. Understanding the molecular mechanisms of pathway regulation is therefore of high interest. Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) comprise a group of protein kinases which are emerging modulators of signal transduction, cell proliferation, survival, and cell differentiation. Work from the last years has identified a close regulatory connection between DYRKs and the Hh signaling system. In this manuscript, we outline the mechanistic influence of DYRK kinases on Hh signaling with a focus on the mammalian situation. We furthermore aim to bring together what is known about the functional consequences of a DYRK-Hh cross-talk and how this might affect cellular processes in development, physiology, and pathology.
      Citation: Journal of Developmental Biology
      PubDate: 2017-11-21
      DOI: 10.3390/jdb5040013
      Issue No: Vol. 5, No. 4 (2017)
  • JDB, Vol. 5, Pages 14: The Hedgehog Signaling Pathway Emerges as a
           Pathogenic Target

    • Authors: Margery Smelkinson
      First page: 14
      Abstract: The Hedgehog (Hh) signaling pathway plays an essential role in the growth, development, and homeostatis of many tissues in vertebrates and invertebrates. Much of what is known about Hh signaling is in the context of embryonic development and tumor formation. However, a growing body of evidence is emerging indicating that Hh signaling is also involved in postnatal processes such as tissue repair and adult immune responses. To that extent, Hh signaling has also been shown to be a target for some pathogens that presumably utilize the pathway to control the local infected environment. In this review, we discuss what is currently known regarding pathogenic interactions with Hh signaling and speculate on the reasons for this pathway being a target. We also hope to shed light on the possibility of using small molecule modulators of Hh signaling as effective therapies for a wider range of human diseases beyond their current use in a limited number of cancers.
      Citation: Journal of Developmental Biology
      PubDate: 2017-11-28
      DOI: 10.3390/jdb5040014
      Issue No: Vol. 5, No. 4 (2017)
  • JDB, Vol. 5, Pages 15: Drosophila as a Model to Study the Link between
           Metabolism and Cancer

    • Authors: Héctor Herranz, Stephen Cohen
      First page: 15
      Abstract: Cellular metabolism has recently been recognized as a hallmark of cancer. Investigating the origin and effects of the reprogrammed metabolism of tumor cells, and identifying its genetic mediators, will improve our understanding of how these changes contribute to disease progression and may suggest new approaches to therapy. Drosophila melanogaster is emerging as a valuable model to study multiple aspects of tumor formation and malignant transformation. In this review, we discuss the use of Drosophila as model to study how changes in cellular metabolism, as well as metabolic disease, contribute to cancer.
      Citation: Journal of Developmental Biology
      PubDate: 2017-12-01
      DOI: 10.3390/jdb5040015
      Issue No: Vol. 5, No. 4 (2017)
  • JDB, Vol. 5, Pages 16: Engineering the Drosophila Genome for Developmental

    • Authors: Dagmara Korona, Stefan Koestler, Steven Russell
      First page: 16
      Abstract: The recent development of transposon and CRISPR-Cas9-based tools for manipulating the fly genome in vivo promises tremendous progress in our ability to study developmental processes. Tools for introducing tags into genes at their endogenous genomic loci facilitate imaging or biochemistry approaches at the cellular or subcellular levels. Similarly, the ability to make specific alterations to the genome sequence allows much more precise genetic control to address questions of gene function.
      Citation: Journal of Developmental Biology
      PubDate: 2017-12-11
      DOI: 10.3390/jdb5040016
      Issue No: Vol. 5, No. 4 (2017)
  • JDB, Vol. 5, Pages 17: The Role of Hedgehog Signalling in the Formation of
           the Ventricular Septum

    • Authors: Antonia Wiegering, Ulrich Rüther, Christoph Gerhardt
      First page: 17
      Abstract: An incomplete septation of the ventricles in the vertebrate heart that disturbes the strict separation between the contents of the two ventricles is termed a ventricular septal defect (VSD). Together with bicuspid aortic valves, it is the most frequent congenital heart disease in humans. Until now, life-threatening VSDs are usually treated surgically. To avoid surgery and to develop an alternative therapy (e.g., a small molecule therapy), it is necessary to understand the molecular mechanisms underlying ventricular septum (VS) development. Consequently, various studies focus on the investigation of signalling pathways, which play essential roles in the formation of the VS. In the past decade, several reports found evidence for an involvement of Hedgehog (HH) signalling in VS development. In this review article, we will summarise the current knowledge about the association between HH signalling and VS formation and discuss the use of such knowledge to design treatment strategies against the development of VSDs.
      Citation: Journal of Developmental Biology
      PubDate: 2017-12-12
      DOI: 10.3390/jdb5040017
      Issue No: Vol. 5, No. 4 (2017)
  • JDB, Vol. 5, Pages 18: Ttc21b Is Required in Bergmann Glia for Proper
           Granule Cell Radial Migration

    • Authors: Ashley Driver, Christopher Shumrick, Rolf Stottmann
      First page: 18
      Abstract: Proper cerebellar development is dependent on tightly regulated proliferation, migration, and differentiation events. Disruptions in any of these leads to a range of cerebellar phenotypes from ataxia to childhood tumors. Animal models have shown that proper regulation of sonic hedgehog (Shh) signaling is crucial for normal cerebellar architecture, and increased signaling leads to cerebellar tumor formation. Primary cilia are known to be required for the proper regulation of multiple developmental signaling pathways, including Shh. Tetratricopeptide Repeat Domain 21B (Ttc21b) is required for proper primary cilia form and function, and is primarily thought to restrict Shh signaling. Here we investigated a role for Ttc21b in cerebellar development. Surprisingly, Ttc21b ablation in Bergmann glia resulted in the accumulation of ectopic granule cells in the lower/posterior lobes of the cerebellum and a reduction in Shh signaling. Ttc21b ablation in just Purkinje cells resulted in a similar phenotype seen in fewer cells, but across the entire extent of the cerebellum. These results suggest that Ttc21b expression is required for Bergmann glia structure and signaling in the developing cerebellum, and in some contexts, augments rather than attenuates Shh signaling.
      Citation: Journal of Developmental Biology
      PubDate: 2017-12-19
      DOI: 10.3390/jdb5040018
      Issue No: Vol. 5, No. 4 (2017)
  • JDB, Vol. 5, Pages 7: A Kinase Duet Performance in the Asymmetric Division
           of Drosophila Neuroblasts

    • Authors: Christopher Johnston
      First page: 7
      Abstract: The ability of progenitor stem cells to divide asymmetrically allows for the production of diverse daughter cell fates.[...]
      Citation: Journal of Developmental Biology
      PubDate: 2017-09-14
      DOI: 10.3390/jdb5030007
      Issue No: Vol. 5, No. 3 (2017)
  • JDB, Vol. 5, Pages 8: The α-Tubulin gene TUBA1A in Brain Development: A
           Key Ingredient in the Neuronal Isotype Blend

    • Authors: Jayne Aiken, Georgia Buscaglia, Emily A. Bates, Jeffrey K. Moore
      First page: 8
      Abstract: Microtubules are dynamic cytoskeletal polymers that mediate numerous, essential functions such as axon and dendrite growth and neuron migration throughout brain development. In recent years, sequencing has revealed dominant mutations that disrupt the tubulin protein building blocks of microtubules. These tubulin mutations lead to a spectrum of devastating brain malformations, complex neurological and physical phenotypes, and even fatality. The most common tubulin gene mutated is the α-tubulin gene TUBA1A, which is the most prevalent α-tubulin gene expressed in post-mitotic neurons. The normal role of TUBA1A during neuronal maturation, and how mutations alter its function to produce the phenotypes observed in patients, remains unclear. This review synthesizes current knowledge of TUBA1A function and expression during brain development, and the brain malformations caused by mutations in TUBA1A.
      Citation: Journal of Developmental Biology
      PubDate: 2017-09-19
      DOI: 10.3390/jdb5030008
      Issue No: Vol. 5, No. 3 (2017)
  • JDB, Vol. 5, Pages 9: Introduction: Drosophila—A Model System for
           Developmental Biology

    • Authors: Nicholas Tolwinski
      First page: 9
      Abstract: Drosophila melanogaster, known colloquially as the fruit fly, remains one of the most commonly used model organisms for biomedical science.[...]
      Citation: Journal of Developmental Biology
      PubDate: 2017-09-20
      DOI: 10.3390/jdb5030009
      Issue No: Vol. 5, No. 3 (2017)
  • JDB, Vol. 5, Pages 4: Moving the Shh Source over Time: What Impact on
           Neural Cell Diversification in the Developing Spinal Cord'

    • Authors: Cathy Danesin, Cathy Soula
      First page: 4
      Abstract: A substantial amount of data has highlighted the crucial influence of Shh signalling on the generation of diverse classes of neurons and glial cells throughout the developing central nervous system. A critical step leading to this diversity is the establishment of distinct neural progenitor cell domains during the process of pattern formation. The forming spinal cord, in particular, has served as an excellent model to unravel how progenitor cells respond to Shh to produce the appropriate pattern. In recent years, considerable advances have been made in our understanding of important parameters that control the temporal and spatial interpretation of the morphogen signal at the level of Shh-receiving progenitor cells. Although less studied, the identity and position of Shh source cells also undergo significant changes over time, raising the question of how moving the Shh source contributes to cell diversification in response to the morphogen. Here, we focus on the dynamics of Shh-producing cells and discuss specific roles for these time-variant Shh sources with regard to the temporal events occurring in the receiving field.
      PubDate: 2017-04-12
      DOI: 10.3390/jdb5020004
      Issue No: Vol. 5, No. 2 (2017)
  • JDB, Vol. 5, Pages 5: Special Issue on HOX Genes in Development

    • Authors: Vincenzo Zappavigna
      First page: 5
      Abstract: n/a
      PubDate: 2017-05-10
      DOI: 10.3390/jdb5020005
      Issue No: Vol. 5, No. 2 (2017)
  • JDB, Vol. 5, Pages 6: Sonic Hedgehog Signaling and Development of the

    • Authors: Maisa Seppala, Gareth Fraser, Anahid Birjandi, Guilherme Xavier, Martyn Cobourne
      First page: 6
      Abstract: Sonic hedgehog (Shh) is an essential signaling peptide required for normal embryonic development. It represents a highly-conserved marker of odontogenesis amongst the toothed vertebrates. Signal transduction is involved in early specification of the tooth-forming epithelium in the oral cavity, and, ultimately, in defining tooth number within the established dentition. Shh also promotes the morphogenetic movement of epithelial cells in the early tooth bud, and influences cell cycle regulation, morphogenesis, and differentiation in the tooth germ. More recently, Shh has been identified as a stem cell regulator in the continuously erupting incisors of mice. Here, we review contemporary data relating to the role of Shh in odontogenesis, focusing on tooth development in mammals and cartilaginous fishes. We also describe the multiple actions of this signaling protein at the cellular level.
      PubDate: 2017-05-31
      DOI: 10.3390/jdb5020006
      Issue No: Vol. 5, No. 2 (2017)
  • JDB, Vol. 5, Pages 1: Acknowledgement to Reviewers of Journal of
           Developmental Biology in 2016

    • Authors: JDB Editorial Office
      First page: 1
      Abstract: n/a
      PubDate: 2017-01-11
      DOI: 10.3390/jdb5010001
      Issue No: Vol. 5, No. 1 (2017)
  • JDB, Vol. 5, Pages 2: Sonic Hedgehog—‘Jack-of-All-Trades’ in Neural
           Circuit Formation

    • Authors: Nikole Zuñiga, Esther Stoeckli
      First page: 2
      Abstract: As reflected by the term morphogen, molecules such as Shh and Wnts were identified based on their role in early development when they instruct precursor cells to adopt a specific cell fate. Only much later were they implicated in neural circuit formation. Both in vitro and in vivo studies indicated that morphogens direct axons during their navigation through the developing nervous system. Today, the best understood role of Shh and Wnt in axon guidance is their effect on commissural axons in the spinal cord. Shh was shown to affect commissural axons both directly and indirectly via its effect on Wnt signaling. In fact, throughout neural circuit formation there is cross-talk and collaboration of Shh and Wnt signaling. Thus, although the focus of this review is on the role of Shh in neural circuit formation, a separation from Wnt signaling is not possible.
      PubDate: 2017-02-08
      DOI: 10.3390/jdb5010002
      Issue No: Vol. 5, No. 1 (2017)
  • JDB, Vol. 5, Pages 3: Canonical Sonic Hedgehog Signaling in Early Lung

    • Authors: Hugo Fernandes-Silva, Jorge Correia-Pinto, Rute Moura
      First page: 3
      Abstract: The canonical hedgehog (HH) signaling pathway is of major importance during embryonic development. HH is a key regulatory morphogen of numerous cellular processes, namely, cell growth and survival, differentiation, migration, and tissue polarity. Overall, it is able to trigger tissue-specific responses that, ultimately, contribute to the formation of a fully functional organism. Of all three HH proteins, Sonic Hedgehog (SHH) plays an essential role during lung development. In fact, abnormal levels of this secreted protein lead to severe foregut defects and lung hypoplasia. Canonical SHH signal transduction relies on the presence of transmembrane receptors, such as Patched1 and Smoothened, accessory proteins, as Hedgehog-interacting protein 1, and intracellular effector proteins, like GLI transcription factors. Altogether, this complex signaling machinery contributes to conveying SHH response. Pulmonary morphogenesis is deeply dependent on SHH and on its molecular interactions with other signaling pathways. In this review, the role of SHH in early stages of lung development, specifically in lung specification, primary bud formation, and branching morphogenesis is thoroughly reviewed.
      PubDate: 2017-03-13
      DOI: 10.3390/jdb5010003
      Issue No: Vol. 5, No. 1 (2017)
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