Similar Datasets
Project description:The cis-regulatory logic integrating spatial and temporal patterning in the vertebrate neural tube
| PRJNA1101103 | ENA
Project description:Secreted signals, known as morphogens, provide the positional information that organizes gene expression and cellular differentiation in many developing tissues. In the vertebrate neural tube, Sonic Hedgehog (Shh) acts as a morphogen to control the pattern of neuronal subtype specification. Using an in vivo reporter of Shh signaling, mouse genetics, and systems modeling, we show that a spatially and temporally changing gradient of Shh signaling is interpreted by the regulatory logic of a downstream transcriptional network. The design of the network, which links three transcription factors to Shh signaling, is responsible for differential spatial and temporal gene expression. In addition, the network renders cells insensitive to fluctuations in signaling and confers hysteresis--memory of the signal. Our findings reveal that morphogen interpretation is an emergent property of the architecture of a transcriptional network that provides robustness and reliability to tissue patterning.
| S-EPMC3267043 | biostudies-other
Project description:Pax3/7 factors play numerous roles in the development of the dorsal nervous system of vertebrates. From specifying neural crest at the neural plate borders, to regulating neural tube closure and patterning of the resulting neural tube. However, it is unclear which of these roles are conserved in non-vertebrate chordates. Here we investigate the expression and function of Pax3/7 in the model tunicate Ciona. Pax3/7 is expressed in neural plate border cells during neurulation, and in central nervous system progenitors shortly after neural tube closure. We find that separate cis-regulatory elements control the expression in these two distinct lineages. Using CRISPR/Cas9-mediated mutagenesis, we knocked out Pax3/7 in F0 embryos specifically in these two separate territories. Pax3/7 knockout in the neural plate borders resulted in neural tube closure defects, suggesting an ancient role for Pax3/7 in this chordate-specific process. Furthermore, knocking out Pax3/7 in the neural impaired Motor Ganglion neuron specification, confirming a conserved role for this gene in patterning the neural tube as well. Taken together, these results suggests that key functions of Pax3/7 in neural tube development are evolutionarily ancient, dating back at least to the last common ancestor of vertebrates and tunicates.
| S-EPMC9511217 | biostudies-literature
Project description:In the Drosophila optic lobes, 800 retinotopically organized columns in the medulla act as functional units for processing visual information. The medulla contains over 80 types of neuron, which belong to two classes: uni-columnar neurons have a stoichiometry of one per column, while multi-columnar neurons contact multiple columns. Here we show that combinatorial inputs from temporal and spatial axes generate this neuronal diversity: all neuroblasts switch fates over time to produce different neurons; the neuroepithelium that generates neuroblasts is also subdivided into six compartments by the expression of specific factors. Uni-columnar neurons are produced in all spatial compartments independently of spatial input; they innervate the neuropil where they are generated. Multi-columnar neurons are generated in smaller numbers in restricted compartments and require spatial input; the majority of their cell bodies subsequently move to cover the entire medulla. The selective integration of spatial inputs by a fixed temporal neuroblast cascade thus acts as a powerful mechanism for generating neural diversity, regulating stoichiometry and the formation of retinotopy.
| S-EPMC5489111 | biostudies-literature
Project description:BackgroundA major goal of computational studies of gene regulation is to accurately predict the expression of genes based on the cis-regulatory content of their promoters. The development of computational methods to decode the interactions among cis-regulatory elements has been slow, in part, because it is difficult to know, without extensive experimental validation, whether a particular method identifies the correct cis-regulatory interactions that underlie a given set of expression data. There is an urgent need for test expression data in which the interactions among cis-regulatory sites that produce the data are known. The ability to rapidly generate such data sets would facilitate the development and comparison of computational methods that predict gene expression patterns from promoter sequence.ResultsWe developed a gene expression simulator which generates expression data using user-defined interactions between cis-regulatory sites. The simulator can incorporate additive, cooperative, competitive, and synergistic interactions between regulatory elements. Constraints on the spacing, distance, and orientation of regulatory elements and their interactions may also be defined and Gaussian noise can be added to the expression values. The simulator allows for a data transformation that simulates the sigmoid shape of expression levels from real promoters. We found good agreement between sets of simulated promoters and predicted regulatory modules from real expression data. We present several data sets that may be useful for testing new methodologies for predicting gene expression from promoter sequence.ConclusionWe developed a flexible gene expression simulator that rapidly generates large numbers of simulated promoters and their corresponding transcriptional output based on specified interactions between cis-regulatory sites. When appropriate rule sets are used, the data generated by our simulator faithfully reproduces experimentally derived data sets. We anticipate that using simulated gene expression data sets will facilitate the direct comparison of computational strategies to predict gene expression from promoter sequence. The source code is available online and as additional material. The test sets are available as additional material.
| S-EPMC2375358 | biostudies-literature
Project description:Neural progenitors alter their output over time to generate different types of neurons and glia in specific chronological sequences, but this process remains poorly understood in vertebrates. Here we show that Casz1, the vertebrate ortholog of the Drosophila temporal identity factor castor, controls the production of mid-/late-born neurons in the murine retina. Casz1 is expressed from mid/late stages in retinal progenitor cells (RPCs), and conditional deletion of Casz1 increases production of early-born retinal neurons at the expense of later-born fates, whereas precocious misexpression of Casz1 has the opposite effect. In both cases, cell proliferation is unaffected, indicating that Casz1 does not control the timing of cell birth but instead biases RPC output directly. Just as Drosophila castor lies downstream of the early temporal identity factor hunchback, we find that the hunchback ortholog Ikzf1 represses Casz1. These results uncover a conserved strategy regulating temporal identity transitions from flies to mammals.
| S-EPMC5912935 | biostudies-literature
Project description:Cis-regulatory changes are thought to play a major role in adaptation. Threespine sticklebacks have repeatedly colonized freshwater habitats in the Northern Hemisphere, where they have evolved a suite of phenotypes that distinguish them from marine populations, including changes in physiology, behavior, and morphology. To understand the role of gene regulatory evolution in adaptive divergence, here we investigate cis-regulatory changes in gene expression between marine and freshwater ecotypes through allele-specific expression (ASE) in F1 hybrids. Surveying seven ecologically relevant tissues, including three sampled across two developmental stages, we identified cis-regulatory divergence affecting a third of genes, nearly half of which were tissue-specific. Next, we compared allele-specific expression in dental tissues at two timepoints to characterize cis-regulatory changes during development between marine and freshwater fish. Applying a genome-wide test for selection on cis-regulatory changes, we find evidence for lineage-specific selection on several processes between ecotypes, including the Wnt signaling pathway in dental tissues. Finally, we show that genes with ASE, particularly those that are tissue-specific, are strongly enriched in genomic regions of repeated marine-freshwater divergence, supporting an important role for these cis-regulatory differences in parallel adaptive evolution of sticklebacks to freshwater habitats. Altogether, our results provide insight into the cis-regulatory landscape of divergence between stickleback ecotypes across tissues and during development, and support a fundamental role for tissue-specific cis-regulatory changes in rapid adaptation to new environments.
| S-EPMC10015619 | biostudies-literature
Project description:Spatial patterning of gene expression is a key process in development, yet how it evolves is still poorly understood. Both cis- and trans-acting changes could participate in complex interactions, so to isolate the cis-regulatory component of patterning evolution, we measured allele-specific spatial gene expression patterns in D. melanogaster × simulans hybrid embryos. RNA-seq of cryo-sectioned slices revealed 66 genes with strong spatially varying allele-specific expression. We found that hunchback, a major regulator of developmental patterning, had reduced expression of the D. simulans allele specifically in the anterior tip of hybrid embryos. Mathematical modeling of hunchback cis-regulation suggested a candidate transcription factor binding site variant, which we verified as causal using CRISPR-Cas9 genome editing. In sum, even comparing morphologically near-identical species we identified surprisingly extensive spatial variation in gene expression, suggesting not only that development is robust to many such changes, but also that natural selection may have ample raw material for evolving new body plans via changes in spatial patterning.
| S-EPMC6211617 | biostudies-literature
Project description:Neural tube closure is a critical morphogenetic event that is regulated by dynamic changes in cell shape and behavior. Although previous studies have uncovered a central role for the non-canonical Wnt signaling pathway in neural tube closure, the underlying mechanism remains poorly resolved. Here, we show that the missing in metastasis (MIM; Mtss1) protein, previously identified as a Hedgehog response gene and actin and membrane remodeling protein, specifically binds to Daam1 and couples non-canonical Wnt signaling to neural tube closure. MIM binds to a conserved domain within Daam1, and this interaction is positively regulated by Wnt stimulation. Spatial expression of MIM is enriched in the anterior neural plate and neural folds, and depletion of MIM specifically inhibits anterior neural fold closure without affecting convergent extension movements or mesoderm cell fate specification. Particularly, we find that MIM is required for neural fold elevation and apical constriction along with cell polarization and elongation in both the superficial and deep layers of the anterior neural plate. The function of MIM during neural tube closure requires both its membrane-remodeling domain and its actin-binding domain. Finally, we show that the effect of MIM on neural tube closure is not due to modulation of Hedgehog signaling in the Xenopus embryo. Together, our studies define a morphogenetic pathway involving Daam1 and MIM that transduces non-canonical Wnt signaling for the cytoskeletal changes and membrane dynamics required for vertebrate neural tube closure.
| S-EPMC3082306 | biostudies-literature
Project description:Planar cell polarity (PCP) controls convergent extension and axis elongation in all vertebrates. Although asymmetric localization of PCP proteins is central to their function, we understand little about PCP protein localization during convergent extension. Here, we use quantitative live imaging to simultaneously monitor cell intercalation behaviors and PCP protein dynamics in the Xenopus laevis neural plate epithelium. We observed asymmetric enrichment of PCP proteins, but more interestingly, we observed tight correlation of PCP protein enrichment with actomyosin-driven contractile behavior of cell-cell junctions. Moreover, we found that the turnover rates of junctional PCP proteins also correlated with the contractile behavior of individual junctions. All these dynamic relationships were disrupted when PCP signaling was manipulated. Together, these results provide a dynamic and quantitative view of PCP protein localization during convergent extension and suggest a complex and intimate link between the dynamic localization of core PCP proteins, actomyosin assembly, and polarized junction shrinking during cell intercalation in the closing vertebrate neural tube.
| S-EPMC6115189 | biostudies-literature