Interplay between morphogen‐directed positional information systems and physiological signaling

Huizar, Francisco J.; Soundarrajan, Dharsan K.; Paravitorghabeh, Ramezan; Zartman, Jeremiah J.

doi:10.1002/dvdy.140

Cited by 15 publications

(18 citation statements)

References 113 publications

(279 reference statements)

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“…where they are in relation to other cells and when to initiate their respective differentiation programs. This idea is captured by the concept of positional information proposed by Wolpert, in which cells acquire information from gradients of external signals or physiological cues such as oxygen or metabolic end products (1,2), which are then translated into spatial developmental patterns (3)(4)(5).…”

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confidence: 99%

Genetic Network Architecture and Environmental Cues Drive Spatial Organization of Phenotypic Division of Labor in Streptomyces coelicolor

Zacharia

Sue

et al. 2021

mBio

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A number of bacteria are known to differentiate into cells with distinct phenotypic traits during processes such as biofilm formation or the development of reproductive structures. These cell types, by virtue of their specialized functions, embody a division of labor. However, how bacteria build spatial patterns of differentiated cells is not well understood. Here, we examine the factors that drive spatial patterns in divisions of labor in colonies of Streptomyces coelicolor, a multicellular bacterium capable of synthesizing an array of antibiotics and forming complex reproductive structures (e.g., aerial hyphae and spores). Using fluorescent reporters, we demonstrate that the pathways for antibiotic biosynthesis and aerial hypha formation are activated in distinct waves of gene expression that radiate outwards in S. coelicolor colonies. We also show that the spatiotemporal separation of these cell types depends on a key activator in the developmental pathway, AdpA. Importantly, when we manipulated local gradients by growing competing microbes nearby, or through physical disruption, expression in these pathways could be decoupled and/or disordered, respectively. Finally, the normal spatial organization of these cell types was partially restored with the addition of a siderophore, a public good made by these organisms, to the growth medium. Together, these results indicate that spatial divisions of labor in S. coelicolor colonies are determined by a combination of physiological gradients and regulatory network architecture, key factors that also drive patterns of cellular differentiation in multicellular eukaryotic organisms. IMPORTANCE Streptomyces coelicolor is a multicellular bacterium that differentiates into specialized cell types and produces a diverse array of natural products. While much is known about the genetic networks that regulate development and antibiotic biosynthesis in S. coelicolor, what drives the spatial organization of these activities within a colony remains to be explored. By using time-lapse microscopy to monitor gene expression in developmental and antibiotic biosynthesis pathways, we found that expression in these pathways occurs in spatiotemporally separated waves. Normally, expression of the antibiotic biosynthesis pathway preceded expression in the developmental pathway; however, this order was compromised in a mutant lacking a key developmental regulator. Furthermore, when we disrupted the local gradients during S. coelicolor growth, we observed disordered patterns of gene expression within colonies. Together, these results indicate that spatial divisions of labor in S. coelicolor colonies are determined by a combination of regulatory network architecture and physiological gradients.

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confidence: 99%

Genetic Network Architecture and Environmental Cues Drive Spatial Organization of Phenotypic Division of Labor in Streptomyces coelicolor

Zacharia

Sue

et al. 2021

mBio

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“…Shape and measurements of the microwell (C). Concentration gradient of morphogen (D,(Huizar, Soundarrajan, Paravitorghabeh, & Zartman, 2020)). Advantage of rounded-tip design of microwell on spheroid formation (E-F).…”

Section: Resultsmentioning

confidence: 99%

“…Thus, compared to other available plate types, there is no need for rinsing solutions that could interfere with cell biology or hamper medical use. It is known, that the concentration of signalling molecules decides the cell fate (schematical representation Figures 1D, F modified by (Huizar et al, 2020). Thus, the tip geometry and coating of the Sphericalplate 5D is designed to support this process.…”

Section: Plate Designmentioning

confidence: 99%

Innovative multidimensional models in a high-throughput-format for different cell types of endocrine origin

Bornstein

Shapiro

Malyukov

et al. 2022

Preprint

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The adrenal gland provides an important function by integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. It is the central organ of the stress response system and has been implicated in numerous stress-related disorders. While for other diseases, regeneration of healthy organ tissue has been aimed at such approaches are lacking for endocrine diseases - with the exception of type-I-diabetes. Moreover, tumor formation is very common, however, appropriate high-throughput applications reflecting the high heterogeneity and furthermore relevant 3D-structures in vitro are still widely lacking. Recently, we have initiated the development of standardized multidimensional models of a variety of endocrine cell/tissue sources in a new multiwell-format. Firstly, we confirmed common applicability for pancreatic pseudo-islets. Next, we translated applicability for spheroid establishment to adrenocortical cell lines as well as patient material to establish spheroids from malignant, but also benign adrenal tumors. We aimed furthermore at the development of bovine derived adrenal organoids and were able to establish steroidogenic active organoids containing both, cells of cortical and medullary origin. Overall, we hope to open new avenues for basic research, endocrine cancer and adrenal tissue-replacement therapies as we demonstrate potential for innovative mechanistic insights and personalized medicine in endocrine (tumor)-biology.

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“…These visual features provide a flat readout of conserved signaling pathway activity ( Figure 1A ; Supplementary Figure S1 ) ( Bier, 2005 ). Wing development is a systems-level process that requires coordinated regulation of cellular processes such as proliferation, differentiation, and morphogenesis ( De Celis, 2003 ; O’Connor et al, 2006 ; Neto-Silva et al, 2009 ; Restrepo et al, 2014 ; Diaz de la Loza and Thompson, 2017 ; Huizar et al, 2020 ). The final shape and size of the adult wing depends on the integration of both intrinsic genetic regulatory networks and extrinsic environmental cues such as temperature, nutrition, and hormones ( Johnston and Gallant, 2002 ; Parker and Struhl, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

MAPPER: An Open-Source, High-Dimensional Image Analysis Pipeline Unmasks Differential Regulation of Drosophila Wing Features

et al. 2022

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Phenomics requires quantification of large volumes of image data, necessitating high throughput image processing approaches. Existing image processing pipelines for Drosophila wings, a powerful genetic model for studying the underlying genetics for a broad range of cellular and developmental processes, are limited in speed, precision, and functional versatility. To expand on the utility of the wing as a phenotypic screening system, we developed MAPPER, an automated machine learning-based pipeline that quantifies high-dimensional phenotypic signatures, with each dimension quantifying a unique morphological feature of the Drosophila wing. MAPPER magnifies the power of Drosophila phenomics by rapidly quantifying subtle phenotypic differences in sample populations. We benchmarked MAPPER’s accuracy and precision in replicating manual measurements to demonstrate its widespread utility. The morphological features extracted using MAPPER reveal variable sexual dimorphism across Drosophila species and unique underlying sex-specific differences in morphogen signaling in male and female wings. Moreover, the length of the proximal-distal axis across the species and sexes shows a conserved scaling relationship with respect to the wing size. In sum, MAPPER is an open-source tool for rapid, high-dimensional analysis of large imaging datasets. These high-content phenomic capabilities enable rigorous and systematic identification of genotype-to-phenotype relationships in a broad range of screening and drug testing applications and amplify the potential power of multimodal genomic approaches.

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Interplay between morphogen‐directed positional information systems and physiological signaling

Cited by 15 publications

References 113 publications

Genetic Network Architecture and Environmental Cues Drive Spatial Organization of Phenotypic Division of Labor in Streptomyces coelicolor

Genetic Network Architecture and Environmental Cues Drive Spatial Organization of Phenotypic Division of Labor in Streptomyces coelicolor

Innovative multidimensional models in a high-throughput-format for different cell types of endocrine origin

MAPPER: An Open-Source, High-Dimensional Image Analysis Pipeline Unmasks Differential Regulation of Drosophila Wing Features

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