BackgroundThe concept of an equivalence group, a cluster of cells with equal potential to adopt the same specific fate, has served as a useful paradigm to understand neural cell type specification. In the Drosophila eye, a set of five cells, called the 'R7 equivalence group', generates a single photoreceptor neuron and four lens-secreting epithelial cells. This choice between neuronal versus non-neuronal cell fates rests on differential requirements for, and cross-talk between, Notch/Delta- and Ras/mitogen-activated protein kinase (MAPK)-dependent signaling pathways. However, many questions remain unanswered related to how downstream events of these two signaling pathways mediate distinct cell fate decisions.ResultsHere, we demonstrate that two direct downstream targets of Ras and Notch signaling, the transcription factors Prospero and dPax2, are essential regulators of neuronal versus non-neuronal cell fate decisions in the R7 equivalence group. Prospero controls high activated MAPK levels required for neuronal fate, whereas dPax2 represses Delta expression to prevent neuronal fate. Importantly, activity from both factors is required for proper cell fate decisions to occur.ConclusionsThese data demonstrate that Ras and Notch signaling are integrated during cell fate decisions within the R7 equivalence group through the combinatorial and opposing activities of Pros and dPax2. Our study provides one of the first examples of how the differential expression and synergistic roles of two independent transcription factors determine cell fate within an equivalence group. Since the integration of Ras and Notch signaling is associated with many developmental and cancer models, these findings should provide new insights into how cell specificity is achieved by ubiquitously used signaling pathways in diverse biological contexts.
Cells must make appropriate fate decisions within a complex and dynamic environment 1. in vitro studies suggest that the cytoskeleton acts as an integrative platform for this environmental input2. External signals regulate cytoskeletal dynamics and the cytoskeleton reciprocally modulates signal transduction3, 4. However, in vivo studies linking cytoskeleton/signaling interactions to embryonic cell fate specification remain limited5-7. Here we show that the cytoskeleton modulates heart progenitor cell fate. Our studies focus on differential induction of heart fate in the basal chordate Ciona intestinalis. We have found that differential induction does not simply reflect differential exposure to the inductive signal. Instead, pre-cardiac cells employ polarized, invasive protrusions to localize their response to an ungraded signal. Through targeted manipulation of the cytoskeletal regulator CDC42, we are able to de-polarize protrusive activity and generate uniform heart progenitor fate specification. Furthermore, we are able to restore differential induction by re-polarizing protrusive activity. These findings illustrate how bi-directional interactions between intercellular signaling and the cytoskeleton can influence embryonic development. In particular, these studies highlight the potential for dynamic cytoskeletal changes to refine cell fate specification in response to crude signal gradients.
Vertebrate rhodopsin promoters exhibit striking sequence identities proximal to the initiation site, suggesting that conserved transcription factors regulate rhodopsin expression in these animals. We identify and characterize two transcriptional activators of the Xenopus rhodopsin gene: homologs of the mammalian Crx and Nrl transcription factors, XOtx5 and XL-Nrl (originally named XL-maf), respectively. XOtx5 stimulated transcription ϳ10-fold in human 293 cells co-transfected with a plasmid containing the rhodopsin promoter (؊508 to ؉41) upstream of luciferase, similar to the ϳ6-fold stimulation with human Crx. XL-Nrl stimulated transcription ϳ27-fold in mammalian 293 cells co-transfected with the rhodopsin luciferase reporter, slightly more than the ϳ17-fold stimulation with Nrl. Together, the Xenopus transcription factors synergistically activated the rhodopsin promoter (ϳ140-fold), as well as in combination with mammalian homologs. Deletion of the Nrl-response element, TGCTGA, eliminated the synergistic activation by both mammalian and Xenopus transcription factors. Deletion of the conserved ATTA sequences (Ret-1 or BAT-1), binding sites for Crx, did not significantly decrease activation by Crx/XOtx5. However, there was increased activation by Nrl/XL-Nrl and an increased synergy when the Ret-1 site was disrupted. These results illustrate conservation of mechanisms of retinal gene expression among vertebrates. In transgenic tadpoles, XOtx5 and XL-Nrl directed premature and ectopic expression from the Xenopus rhodopsin promoter-GFP transgene. Furthermore, activation of the endogenous rhodopsin gene was also observed in some animals, showing that XOtx5 and XL-Nrl can activate the promoter in native chromatin environment.Photoreceptors are highly specialized cells with complex structures that permit efficient light absorption, high signal transduction amplification, rapid kinetics, and adaptation over a range of light intensities (1). Phototransduction requires the coordinated expression of many genes, including the visual pigments that absorb light, enzymes involved in the cGMP cascade, ion channels plus multiple regulatory and structural proteins. It has been estimated using serial analysis of gene expression that ϳ4% of the genes expressed in the retina encode phototransduction proteins (2). Many of these genes are quite conserved in vertebrates. Moreover, programs of eye development share many conserved features in the animal kingdom (3, 4). Even in such distantly related species as Drosophila and humans, similar transcription factors are involved in development and expression of retina-specific genes (5, 6), although the evolutionary significance is not yet settled (5, 7, 8). Often, proteins involved in growth and differentiation of the eye from one species can substitute for homologs in distantly related species (4, 7). This conservation also extends to the cis-acting elements in proximal promoters of retinal genes. Promoters have exhibited at least partial functionality between mammals and lower vertebrate...
Cesium, cadmium, cobalt, and strontium are four contaminants frequently found in soils at biotoxic levels. Introduction of certain nongenetically modified bacteria has been frequently suggested as a method for the immobilization of heavy metal contaminants in soil, thereby reducing runoff and bioavailability. In this study, we have used the polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) to track the survival of five bacterial species added to soil microcosms with and without the addition of a mixture of these metals. The PCR primers targeted conserved regions of the 16S rDNA molecule present in all bacteria. The reaction products were shown to reflect the relative abundance of the bacteria both in mixtures of pure cultures and against a background of all the eubacterial species present in the soil following inoculation. Three of the species (Pseudomonas aeruginosa FRD‐1, Shewanella putrifaciens 200, and Desulfovibrio vulgaris Hildenborough) decreased rapidly following inoculation into both soils. The proportion of Alcaligenes eutrophus CH34 remained at a constant level throughout the 8‐week experiment in both soil treatments. Sphingomonas aromaticivorans B0695 showed toxic metal‐dependent survival in that its relative abundance dropped rapidly in pristine soil but remained at approximately inoculation levels throughout the experiment in contaminated microcosms.
The long-wavelength sensitive (red) opsin genes encode proteins which play a central role in daytime and color vision in vertebrates. We used transgenic Xenopus to identify 5 0 cis-elements in the red cone opsin promoter necessary for cone-specific expression. We found a highly conserved extended region (À725 to À173) that was required for restricting GFP transgene expression to cones. We further identified a short element (5 0 -CCAATTAAG-AGAT-3 0 ) highly conserved amongst tetrapods, including humans, necessary to restrict expression to cones in the retina. These results identify novel conserved elements that regulate spatial expression of tetrapod red cone opsin genes.
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