Cardiopharyngeal deconstruction and ancestral tunicate sessility

AbstractA key problem in understanding chordate evolution has been the origin of sessility of ascidians, and whether the appendicularian free-living style represents a primitive or derived condition of tunicates. To address this problem, we performed comprehensive developmental and genomic comparative analyses of the cardiopharyngeal gene regulatory network (GRN) between appendicularians and ascidians. Our results reveal that the cardiopharyngeal GRN has suffered a process of evolutionary deconstruction with massive ancestral losses of genes (Mesp, Ets1/2, Gata4/5/6, Mek1/2, Tbx1/10, and RA- and FGF-signaling related genes) and subfunctions (e.g. FoxF, Islet, Ebf, Mrf, Dach and Bmp signaling). These losses have led to the deconstruction of two modules of the cardiopharyngeal GRN that in ascidians are related to early and late multipotent state cells involved in lineage fate determination towards first and secondary heart fields, and siphon muscle. Our results allow us to propose an evolutionary scenario, in which the evolutionary deconstruction of the cardiopharyngeal GRN has had an adaptive impact on the acceleration of the developmental cardiac program, the redesign of the cardiac architecture into an open-wide laminar structure, and the loss of pharyngeal muscle. Our findings, therefore, provide evidence supporting that the ancestral tunicate had a sessile ascidian-like lifestyle, and points to the deconstruction of the cardiopharyngeal GRN in appendicularians as a key event that facilitated the evolution of their pelagic free-living style connected to the innovation of the house.

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Brachyury controls Ciona notochord fate as part of a feedforward network and not as a unitary master regulator

10.1101/2020.05.29.124024 ◽

2020 ◽

Cited By ~ 2

Author(s):

Wendy M. Reeves ◽

Kotaro Shimai ◽

Konner M. Winkley ◽

Michael T. Veeman

Keyword(s):

Transcription Factor ◽

Gene Regulatory Network ◽

Regulatory Network ◽

Cell Types ◽

Binding Motif ◽

Fgf Signaling ◽

Feedforward Network ◽

Master Regulator ◽

Gene Regulatory ◽

Direct Activator

AbstractThe notochord is a defining feature of the chordates. The transcription factor Brachyury (Bra) is a key regulator of notochord fate but here we show that it is not a unitary master regulator in the model chordate Ciona. Ectopic Bra expression only partially reprograms other cell types to a notochord-like transcriptional profile and a subset of notochord-enriched genes are unaffected by CRISPR Bra disruption. We identify Foxa.a and Mnx as potential co-regulators and find that combinatorial cocktails are more effective at reprograming other cell types than Bra alone. We reassess the network relationships between Bra, Foxa.a and other components of the notochord gene regulatory network and find that Foxa.a expression in the notochord is regulated by vegetal FGF signaling. It is a direct activator of Bra expression and has a binding motif that is significantly enriched in the regulatory regions of notochord-enriched genes. These and other results indicate that Bra and Foxa.a act together in a regulatory network dominated by positive feed-forward interactions, with neither being a classically-defined master regulator.

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Just Use Distributions: Eliminating The Noise of Sampling-Based Fitness Estimation

10.36227/techrxiv.13042289 ◽

2020 ◽

Author(s):

zhenyue Qin ◽

Tom Gedeon ◽

Robert McKay

Keyword(s):

Gene Regulatory Network ◽

Regulatory Network ◽

Fitness Landscape ◽

Computational Cost ◽

Distributional Analysis ◽

Stochastic Sampling ◽

Evolutionary Scenario ◽

Global Optima ◽

Gene Regulatory

This paper uses distributional analysis to disentangle the effects of fitness landscape and stochasticity in Wagner's Gene Regulatory Network Based evolutionary scenario. Further advantages of the analysis include the ability to accurately identify global optima and potential extensions to approximate the distributional fitness more accurately than stochastic sampling at lower computational cost.<div>This is an inital draft, and will be updated as further content is written.</div>

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Brachyury controls Ciona notochord fate as part of a feedforward network

Development ◽

10.1242/dev.195230 ◽

2021 ◽

pp. dev.195230

Author(s):

Wendy M. Reeves ◽

Kotaro Shimai ◽

Konner M. Winkley ◽

Michael T. Veeman

Keyword(s):

Transcription Factor ◽

Gene Regulatory Network ◽

Regulatory Network ◽

Cell Types ◽

Binding Motif ◽

Fgf Signaling ◽

Feedforward Network ◽

Master Regulator ◽

Gene Regulatory ◽

Direct Activator

The notochord is a defining feature of the chordates. The transcription factor Brachyury (Bra) is a key regulator of notochord fate but here we show that it is not a unitary master regulator in the model chordate Ciona. Ectopic Bra expression only partially reprograms other cell types to a notochord-like transcriptional profile and a subset of notochord-enriched genes are unaffected by CRISPR Bra disruption. We identify Foxa.a and Mnx as potential co-regulators and find that combinatorial cocktails are more effective at reprograming other cell types than Bra alone. We reassess the network relationships between Bra, Foxa.a, and other components of the notochord gene regulatory network and find that Foxa.a expression in the notochord is regulated by vegetal FGF signaling. It is a direct activator of Bra expression and has a binding motif that is significantly enriched in the regulatory regions of notochord-enriched genes. These and other results indicate that Bra and Foxa.a act together in a regulatory network dominated by positive feed-forward interactions, with neither being a classically-defined master regulator.

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The BMP Pathway and Its Inhibitors in the Skeleton

Physiological Reviews ◽

10.1152/physrev.00028.2017 ◽

2018 ◽

Vol 98 (4) ◽

pp. 2431-2452 ◽

Cited By ~ 37

Author(s):

Jonathan W. Lowery ◽

Vicki Rosen

Keyword(s):

Gene Regulatory Network ◽

Regulatory Network ◽

Transforming Growth Factor ◽

Bone Development ◽

Transforming Growth Factor Β ◽

Bmp Signaling ◽

Comprehensive Overview ◽

Organ Systems ◽

Bmp Pathway ◽

Gene Regulatory

Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor-β family of ligands. BMPs exhibit widespread utility and pleiotropic, context-dependent effects, and the strength and duration of BMP pathway signaling is tightly regulated at numerous levels via mechanisms operating both inside and outside the cell. Defects in the BMP pathway or its regulation underlie multiple human diseases of different organ systems. Yet much remains to be discovered about the BMP pathway in its original context, i.e., the skeleton. In this review, we provide a comprehensive overview of the intricacies of the BMP pathway and its inhibitors in bone development, homeostasis, and disease. We frame the content of the review around major unanswered questions for which incomplete evidence is available. First, we consider the gene regulatory network downstream of BMP signaling in osteoblastogenesis. Next, we examine why some BMP ligands are more osteogenic than others and what factors limit BMP signaling during osteoblastogenesis. Then we consider whether specific BMP pathway components are required for normal skeletal development, and if the pathway exerts endogenous effects in the aging skeleton. Finally, we propose two major areas of need of future study by the field: greater resolution of the gene regulatory network downstream of BMP signaling in the skeleton, and an expanded repertoire of reagents to reliably and specifically inhibit individual BMP pathway components.

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