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Title: Deconstruction of the cardiopharyngeal gene regulatory network in appendicularians, a paradigmatic study of Oikopleura dioica as an evolutionary knockout model
Author: Ferrández-Roldán, Alfonso
Director/Tutor: Cañestro García, Cristian
Garcia Fernández, Jordi
Keywords: Genètica
Biologia del desenvolupament
Adaptació (Biologia)
Developmental biology
Adaptation (Biology)
Issue Date: 22-Feb-2021
Publisher: Universitat de Barcelona
Abstract: [eng] The bloom of genomic data has revealed a vast amount of gene losses across all life kingdoms. However, the impact of gene loss on the evolution of the mechanisms of embryo development remains an important challenge. In this work, we have used the successful gene loser Oikopleura dioica, to study the impact of gene loss on the evolution of the cardiopharyngeal gene regulatory network (GRN), and we have extrapolated our results to decipher the ancestral condition of tunicates as free-living or sessile, a hot topic of discussion. To address this question, we have searched for gene losses by combining best reciprocal blast hit (BRBH) with exhaustive phylogenetic reconstructions of the gene family of interest. We have also performed expression analyses of the present orthologs to test for their cardiac function as well as, in the case of lost orthologs, with paralogs trying to detect potential events of function shuffling. Finally, we performed functional analyses by inhibiting the FGF and BMP signaling pathways and started the implementation of a microinjection facility for future functional analyses by gene targeting. Our results show a clear deconstruction of the cardiopharyngeal GRN with the loss of many genes (Mesp, Ets1/2a, Gata4/5/6, Mek1/2, Tbx1/10, and RA- and FGF-signaling related genes) and cardiac subfunctions (FoxF, Islet, Ebf, Mrf, Dach, and Bmp signaling) crucial for cardiopharyngeal development in ascidians and vertebrates. All these losses have led to the dismantling of two genetic modules related to the maintenance of multipotency in the cardiopharyngeal precursors. This has been accompanied by the loss of the second heart field and pharyngeal muscles in appendicularians, which has been phenotypically translated into an open bilaminar heart with an accelerated development compared to the tubular heart present in the rest of chordates. The deconstruction of the cardiopharyngeal GRN in appendicularians can therefore be interpreted as an evolutionary adaptation to the transition from a sessile to a free-living lifestyle based on the innovation of the filter-feeding house. Therefore, our results show O. dioica as a paradigmatic example of the advantages of using species that along their evolution has lost many genes (evolutionary knockout models, eKO) to better understand the evolution of GRNs, mechanisms of embryo development, or any physiological adaptation in the absence of any given gene of interest.
Appears in Collections:Tesis Doctorals - Departament - Genètica, Microbiologia i Estadística

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