scholarly journals TBX5 drives Aldh1a2 expression to regulate a RA-Hedgehog-Wnt gene regulatory network coordinating cardiopulmonary development

2021 ◽  
Author(s):  
Scott A rankin ◽  
Jeffery D Steimle ◽  
Xinan Yang ◽  
Ariel B Rydeen ◽  
Kunal Agarwal ◽  
...  
Keyword(s):  
Heart Development ◽  
Regulatory Networks ◽  
Lateral Plate ◽  
T Box ◽  
Terrestrial Vertebrates ◽  
Regulatory Module ◽  
Evolutionarily Conserved ◽  
Terrestrial Life ◽  
Gene Regulatory ◽  
Foregut Endoderm

The gene regulatory networks that coordinate the development of the cardiac and pulmonary systems are essential for terrestrial life but poorly understood. The T-box transcription factor Tbx5 is critical for both pulmonary specification and heart development, but how these activities are mechanistically integrated remains unclear. We show that Tbx5 regulates an evolutionarily conserved retinoic acid (RA)-Hedgehog-Wnt signaling cascade coordinating cardiopulmonary development. We demonstrate that Tbx5 directly maintains expression of the RA-synthesizing enzyme Aldh1a2 in the foregut lateral plate mesoderm via an intronic enhancer that is evolutionarily conserved among terrestrial vertebrates. Tbx5 promotes posterior second heart field identity in a positive feedback loop with RA, antagonizing a Fgf8-Cyp regulatory module and restricting FGF activity to the anterior. Tbx5/Aldh1a2-dependent RA signaling also directly activates Shh transcription in the adjacent foregut endoderm through the conserved MACS1 enhancer. Epithelial Hedgehog then signals back to the mesoderm, where together with Tbx5 it activates expression of Wnt2/2b that ultimately induce pulmonary fate in the foregut endoderm. These results provide mechanistic insight into the interrelationship between heart and lung development informing cardiopulmonary evolution and birth defects.

scholarly journals Tbx5 drives aldh1a2 expression to regulate a RA-Hedgehog-Wnt gene regulatory network coordinating cardiopulmonary development

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Scott A Rankin ◽  
Jeffrey D Steimle ◽  
Xinan H Yang ◽  
Ariel B Rydeen ◽  
Kunal Agarwal ◽  
...  
Keyword(s):  
Heart Development ◽  
Hedgehog Signaling ◽  
Regulatory Networks ◽  
Lateral Plate ◽  
T Box ◽  
Regulatory Module ◽  
Terrestrial Life ◽  
Heart Field ◽  
Gene Regulatory ◽  
Foregut Endoderm

The gene regulatory networks that coordinate the development of the cardiac and pulmonary systems are essential for terrestrial life but poorly understood. The T-box transcription factor Tbx5 is critical for both pulmonary specification and heart development, but how these activities are mechanistically integrated remains unclear. Here using Xenopus and mouse embryos, we establish molecular links between Tbx5 and retinoic acid (RA)-signaling in the mesoderm and between RA signaling and sonic hedgehog expression in the endoderm to unveil a conserved RA-Hedgehog-Wnt signaling cascade coordinating cardiopulmonary development. We demonstrate that Tbx5 directly maintains expression of aldh1a2, the RA-synthesizing enzyme, in the foregut lateral plate mesoderm via an evolutionarily conserved intronic enhancer. Tbx5 promotes posterior second heart field identity in a positive feedback loop with RA, antagonizing a Fgf8-Cyp regulatory module to restrict FGF activity to the anterior. We find that Tbx5/Aldh1a2-dependent RA signaling directly activates shh transcription in the adjacent foregut endoderm through a conserved MACS1 enhancer. Hedgehog signaling coordinates with Tbx5 in the mesoderm to activate expression of wnt2/2b, which induces pulmonary fate in the foregut endoderm. These results provide mechanistic insight into the interrelationship between heart and lung development informing cardiopulmonary evolution and birth defects.

GATA factors in vertebrate heart development and disease

2006 ◽  
Vol 8 (22) ◽  
pp. 1-20 ◽  
Author(s):  
Alison Brewer ◽  
John Pizzey
Keyword(s):  
Transcription Factors ◽  
Heart Development ◽  
Regulatory Networks ◽  
Cardiac Development ◽  
Cellular Mechanisms ◽  
Cardiac Morphogenesis ◽  
Functional Roles ◽  
Gata Factors ◽  
Evolutionarily Conserved ◽  
Heart Formation

Vertebrate heart formation is dependent upon complex hierarchical gene regulatory networks, which effect both the specification and differentiation of cardiomyocytes and subsequently cardiac morphogenesis. GATA-4, -5 and -6 comprise an evolutionarily conserved subfamily of transcription factors, which are expressed within the precardiac mesoderm from early stages in its specification and continue to be expressed within the adult heart. We review here the functional roles of individual GATA transcription factors in cardiac development, normal homeostasis and disease. We also review the cellular mechanisms employed to regulate the expression and downstream targets of the different GATA factors.

Evolutionarily conserved hierarchical gene regulatory networks for plant salt stress response

Nature Plants ◽  
2021 ◽  
Author(s):  
Ting-Ying Wu ◽  
HonZhen Goh ◽  
Christina B. Azodi ◽  
Shalini Krishnamoorthi ◽  
Ming-Jung Liu ◽  
...  
Keyword(s):  
Salt Stress ◽  
Stress Response ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Salt Stress Response ◽  
Evolutionarily Conserved ◽  
Gene Regulatory

scholarly journals Systematic comparison of sea urchin and sea star developmental gene regulatory networks explains how novelty is incorporated in early development

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Gregory A. Cary ◽  
Brenna S. McCauley ◽  
Olga Zueva ◽  
Joseph Pattinato ◽  
William Longabaugh ◽  
...  
Keyword(s):  
Early Development ◽  
Sea Urchin ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Morphological Diversity ◽  
Sea Star ◽  
Animal Diversity ◽  
Evolutionarily Conserved ◽  
Overall Stability ◽  
Gene Regulatory

AbstractThe extensive array of morphological diversity among animal taxa represents the product of millions of years of evolution. Morphology is the output of development, therefore phenotypic evolution arises from changes to the topology of the gene regulatory networks (GRNs) that control the highly coordinated process of embryogenesis. A particular challenge in understanding the origins of animal diversity lies in determining how GRNs incorporate novelty while preserving the overall stability of the network, and hence, embryonic viability. Here we assemble a comprehensive GRN for endomesoderm specification in the sea star from zygote through gastrulation that corresponds to the GRN for sea urchin development of equivalent territories and stages. Comparison of the GRNs identifies how novelty is incorporated in early development. We show how the GRN is resilient to the introduction of a transcription factor, pmar1, the inclusion of which leads to a switch between two stable modes of Delta-Notch signaling. Signaling pathways can function in multiple modes and we propose that GRN changes that lead to switches between modes may be a common evolutionary mechanism for changes in embryogenesis. Our data additionally proposes a model in which evolutionarily conserved network motifs, or kernels, may function throughout development to stabilize these signaling transitions.

scholarly journals Gene regulatory networks and cell lineages that underlie the formation of skeletal muscle

2017 ◽  
Vol 114 (23) ◽  
pp. 5830-5837 ◽  
Author(s):  
Margaret Buckingham
Keyword(s):  
Skeletal Muscle ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Striated Muscle ◽  
Neck Muscles ◽  
Trunk Muscles ◽  
T Box ◽  
Lineage Tree ◽  
Gene Regulatory ◽  
Myogenic Program

Skeletal muscle in vertebrates is formed by two major routes, as illustrated by the mouse embryo. Somites give rise to myogenic progenitors that form all of the muscles of the trunk and limbs. The behavior of these cells and their entry into the myogenic program is controlled by gene regulatory networks, where paired box gene 3 (Pax3) plays a predominant role. Head and some neck muscles do not derive from somites, but mainly form from mesoderm in the pharyngeal region. Entry into the myogenic program also depends on the myogenic determination factor (MyoD) family of genes, but Pax3 is not expressed in these myogenic progenitors, where different gene regulatory networks function, with T-box factor 1 (Tbx1) and paired-like homeodomain factor 2 (Pitx2) as key upstream genes. The regulatory genes that underlie the formation of these muscles are also important players in cardiogenesis, expressed in the second heart field, which is a major source of myocardium and of the pharyngeal arch mesoderm that gives rise to skeletal muscles. The demonstration that both types of striated muscle derive from common progenitors comes from clonal analyses that have established a lineage tree for parts of the myocardium and different head and neck muscles. Evolutionary conservation of the two routes to skeletal muscle in vertebrates extends to chordates, to trunk muscles in the cephlochordate Amphioxus and to muscles derived from cardiopharyngeal mesoderm in the urochordate Ciona, where a related gene regulatory network determines cardiac or skeletal muscle cell fates. In conclusion, Eric Davidson’s visionary contribution to our understanding of gene regulatory networks and their evolution is acknowledged.

microRNAs in cardiac development and regeneration

2013 ◽  
Vol 125 (4) ◽  
pp. 151-166 ◽  
Author(s):  
Enzo R. Porrello
Keyword(s):  
Gene Expression ◽  
Heart Development ◽  
Regulatory Networks ◽  
Cardiac Development ◽  
Regulation Of Gene Expression ◽  
Cardiac Regeneration ◽  
Cardiac Differentiation ◽  
Evolutionarily Conserved ◽  
Post Transcriptional Regulation ◽  
Therapeutic Possibilities

Heart development involves the precise orchestration of gene expression during cardiac differentiation and morphogenesis by evolutionarily conserved regulatory networks. miRNAs (microRNAs) play important roles in the post-transcriptional regulation of gene expression, and recent studies have established critical functions for these tiny RNAs in almost every facet of cardiac development and disease. The realization that miRNAs are amenable to therapeutic manipulation has also generated considerable interest in the potential of miRNA-based drugs for the treatment of a number of human diseases, including cardiovascular disease. In the present review, I discuss well-established and emerging roles of miRNAs in cardiac development, their relevance to congenital heart disease and unresolved questions in the field for future investigation, as well as emerging therapeutic possibilities for cardiac regeneration.

scholarly journals hrT is required for cardiovascular development in zebrafish

Development ◽  
2002 ◽  
Vol 129 (21) ◽  
pp. 5093-5101 ◽  
Author(s):  
Daniel P. Szeto ◽  
Kevin J. P. Griffin ◽  
David Kimelman
Keyword(s):  
Late Onset ◽  
Cardiovascular Development ◽  
Lateral Plate ◽  
T Box ◽  
Vascular Morphogenesis ◽  
Developing Heart ◽  
Evolutionarily Conserved ◽  
Heart Formation ◽  
Cardiovascular Cells

The recently identified zebrafish T-box gene hrT is expressed in the developing heart and in the endothelial cells forming the dorsal aorta. Orthologs of hrT are expressed in cardiovascular cells fromDrosophila to mouse, suggesting that the function of hrT is evolutionarily conserved. The role of hrT in cardiovascular development, however, has not thus far been determined in any animal model. Using morpholino antisense oligonucleotides, we show that zebrafish embryos lacking hrT function have dysmorphic hearts and an absence of blood circulation. Although the early events in heart formation were normal inhrT morphant embryos, subsequently the hearts failed to undergo looping, and late onset defects in chamber morphology and gene expression were observed. In particular, we found that the loss of hrT function led to a dramatic upregulation of tbx5, a gene required for normal heart morphogenesis. Conversely, we show that overexpression of hrT causes a significant downregulation of tbx5, indicating that one key role ofhrT is to regulate the levels of tbx5. Secondly, we found that HrT is required to inhibit the expression of the blood lineage markersgata1 and gata2 in the most posterior lateral plate mesoderm. Finally, we show that HrT is required for vasculogenesis in the trunk, leading to similar vascular defects to those observed in midline mutants such as floating head. hrT expression in the vascular progenitors depends upon midline mesoderm, indicating that this expression is one important component of the response to a midline-derived signal during vascular morphogenesis.

GNET2: an R package for constructing gene regulatory networks from transcriptomic data

2020 ◽  
Author(s):  
Chen Chen ◽  
Jie Hou ◽  
Xiaowen Shi ◽  
Hua Yang ◽  
James A Birchler ◽  
...  
Keyword(s):  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Data Exchange ◽  
Graphical Model ◽  
R Package ◽  
Supplementary Information ◽  
Original Algorithm ◽  
Transcriptomic Data ◽  
Regulatory Module ◽  
Gene Regulatory

Abstract Motivation The Gene Network Estimation Tool (GNET) is designed to build gene regulatory networks (GRNs) from transcriptomic gene expression data with a probabilistic graphical model. The data preprocessing, model construction and visualization modules of the original GNET software were developed on different programming platforms, which were inconvenient for users to deploy and use. Results Here, we present GNET2, an improved implementation of GNET as an integrated R package. GNET2 provides more flexibility for parameter initialization and regulatory module construction based on the core iterative modeling process of the original algorithm. The data exchange interface of GNET2 is handled within an R session automatically. Given the growing demand for regulatory network reconstruction from transcriptomic data, GNET2 offers a convenient option for GRN inference on large datasets. Availability and implementation The source code of GNET2 is available at https://github.com/jianlin-cheng/GNET2. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Systematic comparison of developmental GRNs explains how novelty is incorporated in early development

2020 ◽  
Author(s):  
Gregory A. Cary ◽  
Brenna S. McCauley ◽  
Olga Zueva ◽  
Joseph Pattinato ◽  
William Longabaugh ◽  
...  
Keyword(s):  
Early Development ◽  
Regulatory Networks ◽  
Morphological Diversity ◽  
Sea Star ◽  
Animal Diversity ◽  
Evolutionarily Conserved ◽  
Overall Stability ◽  
Gene Regulatory ◽  
Embryonic Viability ◽  
Viable Embryo

SUMMARYThe impressive array of morphological diversity among animal taxa represents the product of millions of years of evolution. Morphology is the output of development, therefore phenotypic evolution arises from changes to the topology of the gene regulatory networks (GRNs) that control the highly coordinated process of embryogenesis1. While genetic variation can arise anywhere in the genome and affect any part of an individual GRN, the need to form a viable embryo provides a constraint on the types of variation that pass the filter of selection. A particular challenge in understanding the origins of animal diversity lies in determining how GRNs incorporate novelty while preserving the overall stability of the network, and hence, embryonic viability. Here we assemble a comprehensive GRN, consisting of 42 genes (nodes) and 84 interactions (edges), for the model of endomesoderm specification in the sea star from zygote through gastrulation that corresponds to the GRN for sea urchin development of equivalent territories and stages2. Using these detailed models we make the first systems-level comparison of early development and examine how novelty is incorporated into GRNs. We show how the GRN is resilient to the introduction of a transcription factor, pmar1, the inclusion of which leads to a switch between two stable modes of Delta-Notch signaling. Signaling pathways can function in multiple modes and we propose that GRN changes that lead to switches between modes may be a common evolutionary mechanism for changes in embryogenesis. Our data additionally proposes a model in which evolutionarily conserved network motifs, or kernels, may function throughout development to stabilize these signaling transitions.

Sign in / Sign up

Export Citation Format

Share Document