Dissecting Organismal Morphogenesis by Bridging Genetics and Biophysics

2021 ◽  
Vol 55 (1) ◽  
Author(s):  
Nikhil Mishra ◽  
Carl-Philipp Heisenberg
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Annual Review ◽  
Publication Date ◽  
Technological Advances ◽  
Complex Shapes ◽  
Gene Regulatory ◽  
And Mathematics ◽  
Multicellular Organisms ◽  
Shape Changes

Multicellular organisms develop complex shapes from much simpler, single-celled zygotes through a process commonly called morphogenesis. Morphogenesis involves an interplay between several factors, ranging from the gene regulatory networks determining cell fate and differentiation to the mechanical processes underlying cell and tissue shape changes. Thus, the study of morphogenesis has historically been based on multidisciplinary approaches at the interface of biology with physics and mathematics. Recent technological advances have further improved our ability to study morphogenesis by bridging the gap between the genetic and biophysical factors through the development of new tools for visualizing, analyzing, and perturbing these factors and their biochemical intermediaries. Here, we review how a combination of genetic, microscopic, biophysical, and biochemical approaches has aided our attempts to understand morphogenesis and discuss potential approaches that may be beneficial to such an inquiry in the future. Expected final online publication date for the Annual Review of Genetics, Volume 55 is November 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Beyond Casual Resemblances: Rigorous Frameworks for Comparing Regeneration Across Species

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Mansi Srivastava
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Evolutionary History ◽  
Adult Stem Cells ◽  
Annual Review ◽  
Publication Date ◽  
Animal Phyla ◽  
History Of ◽  
Gene Regulatory ◽  
Unifying Principles

The majority of animal phyla have species that can regenerate. Comparing regeneration across animals can reconstruct the molecular and cellular evolutionary history of this process. Recent studies have revealed some similarity in regeneration mechanisms, but rigorous comparative methods are needed to assess whether these resemblances are ancestral pathways (homology) or are the result of convergent evolution (homoplasy). This review aims to provide a framework for comparing regeneration across animals, focusing on gene regulatory networks (GRNs), which are substrates for assessing process homology. The homology of the wound-induced activation of Wnt signaling and of adult stem cells are discussed as examples of ongoing studies of regeneration that enable comparisons in a GRN framework. Expanding the study of regeneration GRNs in currently studied species and broadening taxonomic sampling for these approaches will identify processes that are unifying principles of regeneration biology across animals. These insights are important both for evolutionary studies of regeneration and for human regenerative medicine. Expected final online publication date for the Annual Review of Cell and Developmental Biology, Volume 37 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Biophysics of Notch Signaling

2021 ◽  
Vol 50 (1) ◽  
Author(s):  
David Sprinzak ◽  
Stephen C. Blacklow
Keyword(s):  
Notch Signaling ◽  
Cell Fate ◽  
Annual Review ◽  
Publication Date ◽  
Dynamic Features ◽  
Signaling Mechanism ◽  
Cell Fate Decisions ◽  
Notch Intracellular Domain ◽  
Numerous Cell ◽  
Multicellular Organisms

Notch signaling is a conserved system of communication between adjacent cells, influencing numerous cell fate decisions in the development of multicellular organisms. Aberrant signaling is also implicated in many human pathologies. At its core, Notch has a mechanotransduction module that decodes receptor–ligand engagement at the cell surface under force to permit proteolytic cleavage of the receptor, leading to the release of the Notch intracellular domain (NICD). NICD enters the nucleus and acts as a transcriptional effector to regulate expression of Notch-responsive genes. In this article, we review and integrate current understanding of the detailed molecular basis for Notch signal transduction, highlighting quantitative, structural, and dynamic features of this developmentally central signaling mechanism. We discuss the implications of this mechanistic understanding for the functionality of the signaling pathway in different molecular and cellular contexts. Expected final online publication date for the Annual Review of Biophysics, Volume 50 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Time-Based Systems Biology Approaches to Capture and Model Dynamic Gene Regulatory Networks

2021 ◽  
Vol 72 (1) ◽  
Author(s):  
Jose M. Alvarez ◽  
Matthew D. Brooks ◽  
Joseph Swift ◽  
Gloria M. Coruzzi
Keyword(s):  
Systems Biology ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Environmental Changes ◽  
Annual Review ◽  
Publication Date ◽  
Learning Approaches ◽  
Dynamic Events ◽  
Genome Wide ◽  
Gene Regulatory

All aspects of transcription and its regulation involve dynamic events. However, capturing these dynamic events in gene regulatory networks (GRNs) offers both a promise and a challenge. The promise is that capturing and modeling the dynamic changes in GRNs will allow us to understand how organisms adapt to a changing environment. The ability to mount a rapid transcriptional response to environmental changes is especially important in nonmotile organisms such as plants. The challenge is to capture these dynamic, genome-wide events and model them in GRNs. In this review, we cover recent progress in capturing dynamic interactions of transcription factors with their targets—at both the local and genome-wide levels—and using them to learn how GRNs operate as a function of time. We also discuss recent advances that employ time-based machine learning approaches to forecast gene expression at future time points, a key goal of systems biology. Expected final online publication date for the Annual Review of Plant Biology, Volume 72 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals GATA-targeted compounds modulate cardiac subtype cell differentiation in dual reporter stem cell line

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mika J. Välimäki ◽  
Robert S. Leigh ◽  
Sini M. Kinnunen ◽  
Alexander R. March ◽  
Ana Hernández de Sande ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Cell Fate ◽  
Reporter Gene ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Fate Decisions ◽  
Dual Reporter ◽  
Gene Regulatory ◽  
Reporter Gene Assays

AbstractBackgroundPharmacological modulation of cell fate decisions and developmental gene regulatory networks holds promise for the treatment of heart failure. Compounds that target tissue-specific transcription factors could overcome non-specific effects of small molecules and lead to the regeneration of heart muscle following myocardial infarction. Due to cellular heterogeneity in the heart, the activation of gene programs representing specific atrial and ventricular cardiomyocyte subtypes would be highly desirable. Chemical compounds that modulate atrial and ventricular cell fate could be used to improve subtype-specific differentiation of endogenous or exogenously delivered progenitor cells in order to promote cardiac regeneration.MethodsTranscription factor GATA4-targeted compounds that have previously shown in vivo efficacy in cardiac injury models were tested for stage-specific activation of atrial and ventricular reporter genes in differentiating pluripotent stem cells using a dual reporter assay. Chemically induced gene expression changes were characterized by qRT-PCR, global run-on sequencing (GRO-seq) and immunoblotting, and the network of cooperative proteins of GATA4 and NKX2-5 were further explored by the examination of the GATA4 and NKX2-5 interactome by BioID. Reporter gene assays were conducted to examine combinatorial effects of GATA-targeted compounds and bromodomain and extraterminal domain (BET) inhibition on chamber-specific gene expression.ResultsGATA4-targeted compounds 3i-1000 and 3i-1103 were identified as differential modulators of atrial and ventricular gene expression. More detailed structure-function analysis revealed a distinct subclass of GATA4/NKX2-5 inhibitory compounds with an acetyl lysine-like domain that contributed to ventricular cells (%Myl2-eGFP+). Additionally, BioID analysis indicated broad interaction between GATA4 and BET family of proteins, such as BRD4. This indicated the involvement of epigenetic modulators in the regulation of GATA-dependent transcription. In this line, reporter gene assays with combinatorial treatment of 3i-1000 and the BET bromodomain inhibitor (+)-JQ1 demonstrated the cooperative role of GATA4 and BRD4 in the modulation of chamber-specific cardiac gene expression.ConclusionsCollectively, these results indicate the potential for therapeutic alteration of cell fate decisions and pathological gene regulatory networks by GATA4-targeted compounds modulating chamber-specific transcriptional programs in multipotent cardiac progenitor cells and cardiomyocytes. The compound scaffolds described within this study could be used to develop regenerative strategies for myocardial regeneration.

Electronic, Ionic, and Mixed Conduction in Polymeric Systems

2021 ◽  
Vol 51 (1) ◽  
Author(s):  
Elayne M. Thomas ◽  
Phong H. Nguyen ◽  
Seamus D. Jones ◽  
Michael L. Chabinyc ◽  
Rachel A. Segalman
Keyword(s):  
Materials Science ◽  
Transport Coefficients ◽  
Polymeric Materials ◽  
Annual Review ◽  
Publication Date ◽  
Energy Storage Devices ◽  
Polymeric Systems ◽  
Storage Devices ◽  
Technological Advances ◽  
Performance Benchmark

Polymers that simultaneously transport electrons and ions are paramount to drive the technological advances necessary for next-generation electrochemical devices, including energy storage devices and bioelectronics. However, efforts to describe the motion of ions or electrons separately within polymeric systems become inaccurate when both species are present. Herein, we highlight the basic transport equations necessary to rationalize mixed transport and the multiscale materials properties that influence their transport coefficients. Potential figures of merit that enable a suitable performance benchmark in mixed conducting systems independent of end application are discussed. Practical design and implementation of mixed conducting polymers require an understanding of the evolving nature of structure and transport with ionic and electronic carrier density to capture the dynamic disorder inherent in polymeric materials. Expected final online publication date for the Annual Review of Materials Science, Volume 51 is July 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Novel generic models for differentiating stem cells reveal oscillatory mechanisms

2021 ◽  
Vol 18 (183) ◽  
Author(s):  
Saeed Farjami ◽  
Karen Camargo Sosa ◽  
Jonathan H. P. Dawes ◽  
Robert N. Kelsh ◽  
Andrea Rocco
Keyword(s):  
Cell Fate ◽  
Regulatory Networks ◽  
Oscillatory Process ◽  
Oscillatory Regime ◽  
Epigenetic Landscape ◽  
Generic Models ◽  
Gene Regulatory ◽  
Oscillatory Mechanisms ◽  
Gradual Variation ◽  
Standard Framework

Understanding cell fate selection remains a central challenge in developmental biology. We present a class of simple yet biologically motivated mathematical models for cell differentiation that generically generate oscillations and hence suggest alternatives to the standard framework based on Waddington’s epigenetic landscape. The models allow us to suggest two generic dynamical scenarios that describe the differentiation process. In the first scenario, gradual variation of a single control parameter is responsible for both entering and exiting the oscillatory regime. In the second scenario, two control parameters vary: one responsible for entering, and the other for exiting the oscillatory regime. We analyse the standard repressilator and four variants of it and show the dynamical behaviours associated with each scenario. We present a thorough analysis of the associated bifurcations and argue that gene regulatory networks with these repressilator-like characteristics are promising candidates to describe cell fate selection through an oscillatory process.

scholarly journals Distinct and overlapping gene regulatory networks in BMP- and HDAC-controlled cell fate determination in the embryonic forebrain

BMC Genomics ◽  
2012 ◽  
Vol 13 (1) ◽  
pp. 298 ◽  
Author(s):  
Catharina Scholl ◽  
Kathrin Weiβmüller ◽  
Pavlo Holenya ◽  
Maya Shaked-Rabi ◽  
Kerry L Tucker ◽  
...  
Keyword(s):  
Cell Fate ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Cell Fate Determination ◽  
Fate Determination ◽  
Overlapping Gene ◽  
Gene Regulatory

scholarly journals Multiple morphogens and rapid elongation promote segmental patterning during development

2021 ◽  
Vol 17 (6) ◽  
pp. e1009077
Author(s):  
Yuchi Qiu ◽  
Lianna Fung ◽  
Thomas F. Schilling ◽  
Qing Nie
Keyword(s):  
Cell Fate ◽  
Gene Regulatory Networks ◽  
Cell Sorting ◽  
Short Range ◽  
Regulatory Networks ◽  
Neural Plate ◽  
Convergent Extension ◽  
Simultaneous Formation ◽  
Gene Regulatory ◽  
Rapid Elongation

The vertebrate hindbrain is segmented into rhombomeres (r) initially defined by distinct domains of gene expression. Previous studies have shown that noise-induced gene regulation and cell sorting are critical for the sharpening of rhombomere boundaries, which start out rough in the forming neural plate (NP) and sharpen over time. However, the mechanisms controlling simultaneous formation of multiple rhombomeres and accuracy in their sizes are unclear. We have developed a stochastic multiscale cell-based model that explicitly incorporates dynamic morphogenetic changes (i.e. convergent-extension of the NP), multiple morphogens, and gene regulatory networks to investigate the formation of rhombomeres and their corresponding boundaries in the zebrafish hindbrain. During pattern initiation, the short-range signal, fibroblast growth factor (FGF), works together with the longer-range morphogen, retinoic acid (RA), to specify all of these boundaries and maintain accurately sized segments with sharp boundaries. At later stages of patterning, we show a nonlinear change in the shape of rhombomeres with rapid left-right narrowing of the NP followed by slower dynamics. Rapid initial convergence improves boundary sharpness and segment size by regulating cell sorting and cell fate both independently and coordinately. Overall, multiple morphogens and tissue dynamics synergize to regulate the sizes and boundaries of multiple segments during development.

Comparative Embryogenesis in Angiosperms: Activation and Patterning of Embryonic Cell Lineages

2021 ◽  
Vol 72 (1) ◽  
Author(s):  
Thomas Dresselhaus ◽  
Gerd Jürgens
Keyword(s):  
Cell Fate ◽  
Embryo Development ◽  
Flowering Plants ◽  
Egg Cell ◽  
Annual Review ◽  
Publication Date ◽  
Zygotic Embryogenesis ◽  
Haploid Induction ◽  
Cell Lineages ◽  
Basic Body

Following fertilization in flowering plants (angiosperms), egg and sperm cells unite to form the zygote, which generates an entire new organism through a process called embryogenesis. In this review, we provide a comparative perspective on early zygotic embryogenesis in flowering plants by using the Poaceae maize and rice as monocot grass and crop models as well as Arabidopsis as a eudicot model of the Brassicaceae family. Beginning with the activation of the egg cell, we summarize and discuss the process of maternal-to-zygotic transition in plants, also taking recent work on parthenogenesis and haploid induction into consideration. Aspects like imprinting, which is mainly associated with endosperm development and somatic embryogenesis, are not considered. Controversial findings about the timing of zygotic genome activation as well as maternal versus paternal contribution to zygote and early embryo development are highlighted. The establishment of zygotic polarity, asymmetric division, and apical and basal cell lineages represents another chapter in which we also examine and compare the role of major signaling pathways, cell fate genes, and hormones in early embryogenesis. Except for the model Arabidopsis, little is known about embryo patterning and the establishment of the basic body plan in angiosperms. Using available in situ hybridization, RNA-sequencing, and marker data, we try to compare how and when stem cell niches are established. Finally, evolutionary aspects of plant embryo development are discussed. Expected final online publication date for the Annual Review of Plant Biology, Volume 72 is May 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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