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The evolutionary origins of regulatory networks that segment the heart into inflow and outflow chambers


Previously, we determined that retinoic acid (RA) signaling synthesized by ALDH1A2/RALDH2 enzyme is crucial for cardiac partition between the units of influx (atria) and efflux (ventricles) in amniote vertebrates. We propose to: 1) investigate the controversial role of RA signaling in teleost to define if RA signaling is, or not, an ancestral mechanism for the partition of the influx/efflux heart domains in all vertebrates; 2) define the origins of atrial signaling mechanisms that operate on the Slow Myosin Heavy Chain III (SMyHC III) gene and characterize regulatory networks of atrial development; 3) establish the relationship between structure and function of the different aldehyde dehydrogenases (ALDHs) from chordates invertebrates such as Branchiostoma floridae and Ciona intestinalis to characterize the ALDHs transition between the functions of detoxification and signaling (via RA production) and, consequently, to understand the evolutionary origins of the signals underlying vertebrate heart segmentation into influx and efflux units. The major challenges are: a) to use all the potential of the zebrafish model (Danio rerio) to understand the cardiac segmentation into influx/efflux units; b) to embrace the proteomic approach in development and c) to install the know-how for expression and biochemical analyses of ALDHs. Our commitments include: to offer an infrastructure for using the zebrafish as a model organism, to produce original scientific manuscripts and reviews, to train graduate students and to diffuse knowledge on Developmental Biology and Evolution through the participation in academic meetings and training events. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
XAVIER-NETO, JOSE; CARVALHO, MURILO; PASCOALINO, BRUNO DOS SANTOS; CARDOSO, ALISSON CAMPOS; SOUSA COSTA, ANGELA MARIA; MACEDO PEREIRA, ANA HELENA; SANTOS, LUANA NUNES; SAITO, ANGELA; MARQUES, RAFAEL ELIAS; COSTA SMETANA, JULIANA HELENA; et al. Hydrocephalus and arthrogryposis in an immunocompetent mouse model of ZIKA teratogeny: A developmental study. PLoS Neglected Tropical Diseases, v. 11, n. 2, . (13/22695-0)

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