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Results for “Developmental Biology”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 181 records · Page 10Linked to original sources

bioRxiv2015

Oxygen changes drive non-uniform scaling in Drosophila melanogaster embryogenesis

In Drosophila embryogenesis, increasing either oxygen concentration or temperature accelerates development. Having previously investigated temperatures impact on embryogenesis, we characterized developmental response to oxygen levels using time-lapse imaging. Changing oxygen concentrations greatly impact survival, with developmental rate changes that are dwarfed by those induced by temperature. While extreme temperatures increase early embryo mortality, mild hypoxia increases arrest and death during mid-embryogenesis and mild hyperoxia increases survival over normoxia. Though not independent, the reactions to temperature and oxygen are fundamentally different, with developmental time being inversely proportional to oxygen concentration but logarithmically related to temperature. Most notably, while development scales uniformly with temperature, oxygen changes drive developmental heterochrony. Morphological processes change with oxygen concentration at different rates. Gut formation is more severely slowed by decreases in oxygen, while head involution and syncytial development are less impacted than the rest of development. These data reveal that uniform scaling, seen with changes in temperature, is not the default result of adjusting developmental rate.

Developmental Biology↗

bioRxiv2015

The beetle amnion and serosa functionally interact as apposed epithelia

Unlike passive rupture of the human chorioamnion at birth, the insect extraembryonic (EE) tissues - the amnion and serosa - actively rupture and withdraw in late embryogenesis. Despite its importance for successful development, EE morphogenesis remains poorly understood. Contradicting the hypothesis of a single, fused EE membrane, we show that both tissues persist as discrete epithelia within a bilayer, using new tissue-specific EGFP transgenic lines in the beetle Tribolium castaneum. Quantitative live imaging analyses show that the amnion initiates EE rupture in a specialized anterior-ventral cap, while RNAi manipulation of EE tissue complement and function reveals that the serosa is autonomously contractile. Thus the bilayer efficiently coordinates the amnion as initiator and serosa as driver to achieve withdrawal. The novel bilayer architecture may reflect evolutionary changes in the EE tissues specific to holometabolous insects. More generally, tissue apposition in a bilayer exemplifies a high degree of functional interaction between developing epithelia.

Developmental Biology↗

bioRxiv2015

Species Tailoured Contribution of Volumetric Growth and Tissue Convergence to Posterior Body Elongation in Vertebrates

Axial elongation is a widespread mechanism propelling the generation of the metazoan body plan. A widely accepted model is that of posterior growth, where new tissue is continually added from the posterior unsegmented tip of the body axis. A key question is whether or not such a posterior growth zone generates sufficient additional tissue volume to generate elongation of the body axis, and the degree to which this is balanced with tissue convergence and/or growth in already segmented regions of the body axis. We applied a multi-scalar morphometric analysis during posterior axis elongation in zebrafish. Importantly, by labelling of specific regions/tissues and tracking their deformation, we observed that the unsegmented region does not generate additional tissue volume at the caudal tip. Instead, it contributes to axis elongation by extensive tissue deformation at constant volume. We show that volumetric growth occurs in the segmented portion of the axis and can be attributed to an increase in the size and length of the spinal cord and notochord. FGF inhibition blocks tissue convergence within the tailbud and unsegmented region rather than affecting volumetric growth, showing that a conserved molecular mechanism can control convergent morphogenesis, even if by different cell behaviours. Finally, a comparative morphometric analysis in lamprey, dogfish, zebrafish and mouse reveal a differential contribution of volumetric growth that is linked to a switch between external and internal modes of development. We propose that posterior growth is not a conserved mechanism to drive axis elongation in vertebrates. It is instead associated with an overall increase in growth characteristic of internally developing embryos that undergo embryonic development concomitantly with an increase in energy supply from the female parent.

Developmental Biology↗

bioRxiv2015

Glial and neuronal Semaphorin signaling instruct the development of a functional myotopic map for Drosophila walking

Motoneurons developmentally acquire appropriate cellular architectures that ensure connections with postsynaptic muscles and presynaptic neurons. In Drosophila, leg motoneurons are organized as a myotopic map, where their dendritic domains represent the muscle field. Here we investigate mechanisms underlying development of aspects of this myotopic map, required for walking. A behavioral screen identified roles for Semaphorins (Serna) and Plexins (Plex) in walking behavior. Deciphering this phenotype, we show that PlexA/Sema1a mediates motoneuron axon branching in ways that differ in the proximal femur and distal tibia, based on motoneuronal birth order. Importantly, we show a novel role for glia in positioning dendrites of specific motoneurons; PlexB/Sema2a is required for dendritic positioning of late-born motoneurons but not early-born motoneurons. These findings indicate that communication within motoneurons and between glia and motoneurons, mediated by the combined action of different Plexin/Semaphorin signaling systems, are required for the formation of a functional myotopic map.

Developmental Biology↗

bioRxiv2015

Expansion of haematopoietic stem cells during development

Haematopoietic stem cells (HSCs) arise in the embryo in the aorta-gonad-mesonephros region and the placenta, afterwards colonise the liver (and spleen) and finally the bone marrow, which, from birth on, remains the sole site of haematopoiesis. In mouse, after the fetal phase of rapid HSCs expansion, the number of these stem cells continues to increase after birth in order to sustain the growing blood volume of the developing infant. The number of total circulating reticulocytes seems to indicate that this growth stops around the third week of murine life, well before the whole animal stops to grow. Around the same time, a period of abundant lymphopoiesis ends. Human HSCs seem to show similar patterns during post-natal growth and these could be useful to understand the peculiar features of paediatric leukaemogenesis.

Developmental Biology↗

bioRxiv2015

The zebrafish goosepimples/myosin Vb mutant exhibits cellular attributes of human microvillus inclusion disease

BackgroundMicrovillus inclusion disease (MVID) is a life threatening enteropathy characterised by perpetual diarrhoea. Recent analysis has revealed that enterocytes in MVID patients exhibit reduction of microvilli, presence of microvillus inclusion bodies and intestinal villus atrophy. Genetic linkage analysis has identified mutations in myosin Vb gene as the main cause of MVID. An animal model that develops ex-utero and is tractable genetically as well as by microscopy would be highly useful to study the cellular basis of the formation of inclusion bodies.\n\nResultsHere we report that the intestine of the zebrafish goosepimples (gsp)/myosin Vb (myoVb) mutant show severe reduction in the intestinal folds-structures similar to mammalian villi. The loss of folds is further correlated with changes in the shape of enterocytes. In a striking similarity with MVID patients, zebrafish gsp/myoVb mutant larvae exhibit microvillus atrophy, microvillus inclusions and accumulation of secretory material in enterocytes.\n\nConclusionWe propose that the zebrafish gsp/myoVb mutant is a valuable model to study the pathophysiology of MVID. Owing to the advantages of zebrafish in screening libraries of small molecules, the gsp mutant will be an appropriate tool to identify compounds that would alleviate the formation of microvillus inclusions and have therapeutic value.

Developmental Biology↗

bioRxiv2015

Dynamic stem cell states: naive to primed pluripotency in rodents and humans

PrefaceThe molecular mechanisms and signalling pathways that regulate the in vitro preservation of distinct pluripotent stem cell configurations, and their induction in somatic cells via direct reprogramming approaches, continue to constitute a highly exciting area of research. In this review, we provide an integrative synthesis on recent discoveries related to isolating unique naive and primed pluripotent stem cell states with altered functional and molecular characteristics, and from different species. We overview pathways underlying pluripotent state transitions and interconversion in vitro and in vivo. We conclude by highlighting unresolved key questions, future directions and potential novel applications of such dynamic pluripotent cell states.

Developmental Biology↗

bioRxiv2015

Assisted reproduction causes intrauterus growth restriction by disrupting placental lipid metabolism

IVF related intrauterus growth restriction or low birth weight (LBW) is very common in ART clinic. This study is focus on the aberrant lipid metabolism induced by in vitro fertilization and its mechanism. Firstly, we investigated the effect of IVF on fetal weight and placenta efficiency at E18.5 (at birth) and E14.5 (middle gestation). Data shows that IVF caused LBW and low placenta efficiency. Then we studied the lipidomics of E18.5 placenta and E14.5 placenta. The IVF group has an eccentric lipid content compared to in vivo group. All the 15 lipid classes are largely accumulated in E18.5 IVF placenta and are deficient in E14.5 IVF placenta. In detail, most of the 287 lipid species is accumulated at E18.5 and went short at E14.5. Using qRT-PCR we detected the expression level of genes related to lipid uptake, transport and metabolism. Most of these genes are down-regulated which indicated the metabolism function of placenta is disrupted seriously. To the imprinted genes for lipid metabolism regulation as GNAS and Grb10, IVF not only disrupt their imprinting status (methylation level) but also disrupt their gene expression. The expression of DNMTs and Tets are also disrupted in the placenta. These data demonstrate that IVF impaired the regulation network of lipid metabolism. These results prove the hypothesis: imperfect IVF condition of fertilization jeopardize the expression DNMTs, Tets and imprinting status of imprinted genes for lipid metabolism regulation. Then it causes to abnormal expression of genes for lipid metabolism and regulation. This leads to the significant differences in lipid species quantification and lipid metabolism. So it contributed to low lipid transport efficiency, restricted fetal growth and LBW. This study provides a renewed knowledge of lipid metabolism in placenta and its relation to imprinted genes and gave some clinical aware for optimizing the ART practice.\n\nFundingThis work was supported by grants from the National Basic Research Program of China (973 Program) and National Natural Science Foundation of China.\n\nCompeting InterestsThe authors have declared that no competing interests exist.\n\nAbbreviations

Developmental Biology↗

bioRxiv2015

Towards a study of gene regulatory constraints to morphological evolution of the Drosophila ocellar region

The morphology and function of organs depend on coordinated changes in gene expression during development. These changes are controlled by transcription factors, signaling pathways and their regulatory interactions, which are represented by gene regulatory networks (GRNs). Therefore, the structure of an organ GRN restricts the morphological and functional variations that the organ can experience -its potential morphospace. Therefore, two important questions arise when studying any GRN: what is the predicted available morphospace and what are the regulatory linkages that contribute the most to control morphological variation within this space. Here, we explore these questions by analyzing a small \"3-node\" GRN model that captures the Hh-driven regulatory interactions controlling a simple visual structure: the ocellar region of Drosophila. Analysis of the model predicts that random variation of model parameters results in a specific non-random distribution of morphological variants. Study of a limited sample of Drosophilids and other dipterans finds a correspondence between the predicted phenotypic range and that found in nature. As an alternative to simulations, we apply Bayesian Networks methods in order to identify the set of parameters with the largest contribution to morphological variation. Our results predict the potential morphological space of the ocellar complex, and identify likely candidate processes to be responsible for ocellar morphological evolution using Bayesian networks. We further discuss the assumptions that the approach we have taken entails and their validity.

Developmental Biology↗

bioRxiv2015

Diversity of fate outcomes in cell pairs under lateral inhibition

Cell fate determination by lateral inhibition via Notch/Delta signalling has been extensively studied. Most formalised models consider Notch/Delta interactions in fields of cells, with parameters that typically lead to symmetry breaking of signalling states between neighbouring cells, commonly resulting in salt-and-pepper fate patterns. Here we consider the case of signalling between isolated cell pairs, and find that the bifurcation properties of a standard mathematical model of lateral inhibition can lead to stable symmetric signalling states. We apply this model to the adult intestinal stem cell (ISC) of Drosophila, whose fate is stochastic but dependent on the Notch/Delta pathway. We observe a correlation between signalling state in cell pairs and their contact area. We interpret this behaviour in terms of the properties of our model in the presence of population variability in signalling thresholds. Our results suggest that the dynamics of Notch/Delta signalling can contribute to explain stochasticity in stem cell fate decisions, and that the standard model for lateral inhibition can account for a wider range of developmental outcomes than previously considered.\n\nSummary statementNotch/Delta-mediated lateral inhibition in cell pairs can result in symmetric signalling depending on the activation threshold, which can modulate cell-fate decisions depending on contact area.

Developmental Biology↗

bioRxiv2015

DISC1 regulates astrogenesis in the embryonic brain via modulation of RAS/MEK/ERK signaling through RASSF7

Disrupted in Schizophrenia1 (DISC1) is known as a high susceptibility gene of schizophrenia. More recent studies have connected schizophrenia with glia defects and dysfunction. However, it is unclear whether there is connection between DISC1 and gliogenesis defect. Thus, a precise understanding of DISC1 (a ubiquitously expressed brain protein) on astrogenesis in the late stage of embryonic mouse brain development needs to be deeply investigated. Here, we show that suppression of DISC1 expression represses astrogenesis in vitro and in vivo, whereas DISC1 overexpression substantially enhances the process. Furthermore, mouse and human DISC1 overexpression rescued astrogenesis defects caused by DISC1 knowndown. Mechanistically, DISC1 activates downstream RAS/MEK/ERK signaling pathway via directly associating with the C terminal domain of RASSF7, a RAS association protein. Also, the pERK complex undergoes nuclear translocation and influences the expression of genes related to astrogenesis. Briefly, our results demonstrate that DISC1 regulates astrogenesis by modulating RAS/MEK/ERK signaling via RASSF7 and provide a framework for understanding how DISC1 dysfunction leads to neuropsychiatric diseases.

Developmental Biology↗

bioRxiv2015

Polarized Cortical Tension drives Zebrafish Epiboly Movements

The physical principles underlying the biomechanics of morphogenetic processes are largely unknown. Epiboly is an essential embryonic event in which three distinct tissues coordinate to direct the expansion of the blastoderm. How and where forces are generated during epiboly and how these are globally coupled remains elusive. Here we first develop a method, Hydrodynamic Regression (HR), to infer 3D dynamic pressure fields, mechanical power densities and cortical surface tension profiles within living organisms. HR is based on velocity measurements retrieved from 2D+T microscopy time-lapses and their hydrodynamic modeling. We then applied this method to identify biomechanically active structures during epiboly in the zebrafish and the changes in the distribution of cortex local tension as epiboly progresses. Based on these results, we propose a novel simple physical description for epiboly, where tissue movements are directed by a polarized gradient of cortical tension. We found that this tensional gradient relies on local contractile forces at the cortex, differences in the elastic properties of cortex components and force passive transmission within the incompressible yolk cell. All in all, our work identifies a novel way to physically regulate concerted cellular movements that will be fundamental for the mechanical control of many morphogenetic processes.

Developmental Biology↗

bioRxiv2015

The relaxin receptor Lgr3 mediates growth coordination and developmental delay during Drosophila melanogaster imaginal disc regeneration

Damage to Drosophila melanogaster imaginal discs activates a regeneration checkpoint that 1) extends larval development and 2) coordinates the regeneration of the damaged disc with the growth of undamaged discs. These two systemic responses to damage are both mediated by Dilp8, a member of the insulin/IGF/relaxin family of peptide hormones, which is released by regenerating imaginal discs. Growth coordination between regenerating and undamaged imaginal discs is dependent on Dilp8 activation of NOS in the prothoracic gland (PG), which slows the growth of undamaged discs by limiting ecdysone synthesis. Here we demonstrate that the Drosophila relaxin receptor homologue Lgr3, a leucine-rich repeat-containing G-protein coupled receptor, is required for Dilp8-dependent growth coordination and developmental delay during the regeneration checkpoint. Lgr3 regulates these responses to damage via distinct mechanisms in different tissues. Using tissue-specific RNAi disruption of Lgr3 expression, we show that Lgr3 functions in the PG upstream of nitric oxide synthase (NOS), and is necessary for NOS activation and growth coordination during the regeneration checkpoint. When Lgr3 is depleted from neurons, imaginal disc damage no longer produces either developmental delay or growth inhibition. To reconcile these discrete tissue requirements for Lgr3 during regenerative growth coordination, we demonstrate that Lgr3 activity in the both the CNS and PG is necessary for NOS activation in the PG following damage. Together, these results identify new roles for a relaxin receptor in mediating damage signaling to regulate growth and developmental timing.

Developmental Biology↗

bioRxiv2015

Increased avidity for Dpp/BMP2 maintains the proliferation of eye progenitors in Drosophila

During normal organ development, the progenitor cell state is transient: it depends on specific combinations of transcription factors and extracellular signals, that cooperate to sustain the proliferative potential and undifferentiated status of organ progenitor cells. Not surprisingly, abnormal maintenance of progenitor transcription factors may lead to tissue overgrowth, and the concurrence of specific signals from the local environment is often critical to trigger this overgrowth. Therefore, the identification of the specific combinations of transcription factors and signals that promote or oppose proliferation in progenitor cells is essential to understand normal development and disease. We have investigated this issue by asking what signals may promote the proliferation of eye progenitors in Drosophila. Two transcription factors, the MEIS1 homologue homothorax (hth) and the Zn-finger teashirt (tsh) are transiently expressed in eye progenitors causing the expansion of the progenitor pool. However, if their co-expression is maintained experimentally, cell proliferation continues and differentiation is halted. Here we show that Hth+Tsh-induced tissue overgrowth requires the BMP2 ligand Dpp and the activation of its pathway. In Hth+Tsh cells, the Dpp pathway is abnormally hyperactivated. Rather than using autocrine Dpp expression, Hth+Tsh cells increase their avidity for Dpp, produced locally, by upregulating extracellular matrix components. During normal development, Dpp represses hth and tsh ensuring that the progenitor state is transient. However, cells in which Hth+Tsh expression is maintained use Dpp to enhance their proliferation.\n\nSummary StatementIn Drosophila, homothorax, the Meis1 homologue, and teashirt jointly sustain the proliferation of eye progenitor cells by increasing their avidity for BMP produced by the local microenvironment.

Developmental Biology↗

bioRxiv2015

The Drosophila Neurogenin, Tap, controls axonal growth through the Wnt adaptor protein Dishevelled

The Neurogenin (Ngn) transcription factors control early neurogenesis and neurite outgrowth in mammalian cortex. In contrast to their proneural activity, their function in neurite growth is poorly understood. Drosophila has a single predicted Ngn homologue called Tap, whose function is completely unknown. Here we show that Tap is not a proneural protein in Drosophila but is required for proper axonal growth and guidance of neurons of the mushroom body (MB), a neuropile required for associative learning and memory. Genetic and expression analyses suggest that Tap inhibits excessive axonal growth by fine regulation of the levels of the Wnt signaling adaptor protein, Dishevelled.\n\nSummaryThe Drosophila Neurogenin homologue, Target of Pox neuro (Tap), prevents axonal overgrowth by regulating the Wnt Planar Cell Polarity pathway adaptor protein Dishevelled.

Developmental Biology↗

bioRxiv2016

A Notch and Su(H) dependent enhancer complex coordinates expression of nab in Drosophila

ABTRACTThe transcription factor Suppressor of Hairless and its co-activator, the Notch intracellular domain, are polyglutamine (pQ)-rich factors that target enhancer elements and interact with other locally-bound pQ-rich factors. To understand the functional repertoire of such enhancers, we identify conserved regulatory belts with binding sites for the pQ-rich effectors of both Notch and BMP/Dpp signaling, and the pQ-deficient tissue selectors Apterous (Ap), Scalloped (Sd), and Vestigial (Vg). We find that the densest such binding site cluster in the genome is located in the BMP-inducible nab locus, a homolog of the vertebrate transcriptional co-factors NAB1/NAB2. We report three major findings. First, we find that this nab regulatory belt is a novel enhancer driving dorsal wing margin expression in regions of peak phosphorylated-Mad in wing imaginal discs. Second, we show that Ap is developmentally required to license the nab dorsal wing margin enhancer (DWME) to read-out Notch signaling in the dorsal wing compartment. Third, we find that the nab DWME is embedded in a complex of intronic enhancers, including a wing quadrant enhancer, a proximal wing disc enhancer, and a larval brain enhancer. This enhancer complex coordinates global nab expression via both tissue-specific activation and inter-enhancer silencing. We suggest that DWME integration of BMP signaling maintains nab expression in proliferating margin descendants that have divided away from Notch-Delta boundary signaling. As such, uniform expression of genes like nab and vestigial in proliferating compartments would typically require both boundary and non-boundary lineage-specific enhancers.

Developmental Biology↗

bioRxiv2016

Identification and Functional Characterization of Muscle Satellite Cells in Drosophila

Work on genetic model systems such as Drosophila and mouse has shown that the fundamental mechanisms of myogenesis are remarkably similar in vertebrates and invertebrates. Strikingly, however, satellite cells, the adult muscle stem cells that are essential for the regeneration of damaged muscles in vertebrates, have not been reported in invertebrates. In this study we show role of Muscle stem cells (Gunage et al., 2014) identified in a previous study, in muscle regeneration. We show that muscle stem cells lineal descendants are present in adult muscle as small, unfused cells located superficially and in close proximity to the mature muscle fibers. Normally quiescent cells, following muscle fiber injury become mitotically active, engage in Notch-Delta signaling-dependent proliferative activity and generate lineal descendant populations, which fuse with the injured muscle fiber. In view of their strikingly similar morphological and functional features, we consider these novel cells to be Drosophila muscle satellite cells

Developmental Biology↗

bioRxiv2016

Rules of tissue packing involving different cell types: human muscle organization

Natural packed tissues are assembled as tessellations of polygonal cells that do not leave empty spaces between them. They include the epithelial sheets and the skeletal muscles. Epithelia are formed by equivalent cells that change shape and organization through development. The skeletal muscles appear as a mosaic composed by two different types of cells: the slow and fast fibres that are determined by the identities of the motor neurons that innervate them. Their relative distribution is important for the muscle function and can be altered in some neuromuscular diseases. Little is known about how the spatial organization of fast and slow fibres is established and maintained. In this work we use computerized image analysis and mathematical concepts to capture the organizational pattern in two different healthy muscles: biceps brachii and quadriceps. Here we show that each type of muscle portrays a characteristic topological pattern that allows distinguishing between them. The biceps brachii muscle presents a particular arrange based on the different size of slow and fast fibres, contrary to the quadriceps muscle where an unbiased distribution exists. Our results indicate that the relative size of each cellular type imposes an intrinsic organization into the tissue. These findings establish a new framework for the analysis of packed tissues where two or more cell types exist.

Developmental Biology↗