title: Signaling through retinoic acid receptors in cardiac development: Doing the right things at the right times.
abstract: Retinoic acid (RA) is a terpenoid that is synthesized from vitamin A/retinol (ROL) and binds to the nuclear receptors retinoic acid receptor (RAR)/retinoid X receptor (RXR) to control multiple developmental processes in vertebrates. The available clinical and experimental data provide uncontested evidence for the pleiotropic roles of RA signaling in development of multiple embryonic structures and organs such eyes, central nervous system, gonads, lungs and heart. The development of any of these above-mentioned embryonic organ systems can be effectively utilized to showcase the many strategies utilized by RA signaling. However, it is very likely that the strategies employed to transfer RA signals during cardiac development comprise the majority of the relevant and sophisticated ways through which retinoid signals can be conveyed in a complex biological system. Here, we provide the reader with arguments indicating that RA signaling is exquisitely regulated according to specific phases of cardiac development and that RA signaling itself is one of the major regulators of the timing of cardiac morphogenesis and differentiation. We will focus on the role of signaling by RA receptors (RARs) in early phases of heart development. This article is part of a Special Issue entitled: Nuclear receptors in animal development.
authors.affiliation: Brazilian Biosciences National Laboratory, Brazilian Center of Research in Energy and Materials, Rua Giuseppe Máximo Scolfaro, 10.000, Campinas, SP CEP 13083-970, Brazil. Electronic address: xavier.neto@lnbio.cnpem.br.
authors.forename: José
authors.initials: J
authors.lastname: Xavier-Neto
authors.affiliation: Brazilian Biosciences National Laboratory, Brazilian Center of Research in Energy and Materials, Rua Giuseppe Máximo Scolfaro, 10.000, Campinas, SP CEP 13083-970, Brazil. Electronic address: angela.costa@lnbio.cnpem.br.
authors.forename: Ângela M
authors.initials: ÂM
authors.lastname: Sousa Costa
authors.affiliation: Brazilian Biosciences National Laboratory, Brazilian Center of Research in Energy and Materials, Rua Giuseppe Máximo Scolfaro, 10.000, Campinas, SP CEP 13083-970, Brazil. Electronic address: ana.figueira@lnbio.cnpem.br.
authors.forename: Ana Carolina M
authors.initials: AC
authors.lastname: Figueira
authors.affiliation: Brazilian Biosciences National Laboratory, Brazilian Center of Research in Energy and Materials, Rua Giuseppe Máximo Scolfaro, 10.000, Campinas, SP CEP 13083-970, Brazil. Electronic address: donato.caiaffa@lnbio.cnpem.br.
authors.forename: Carlo Donato
authors.initials: CD
authors.lastname: Caiaffa
authors.affiliation: Brazilian Biosciences National Laboratory, Brazilian Center of Research in Energy and Materials, Rua Giuseppe Máximo Scolfaro, 10.000, Campinas, SP CEP 13083-970, Brazil; Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address: fabio.amaral@lnbio.cnpem.br.
authors.forename: Fabio Neves do
authors.initials: FN
authors.lastname: Amaral
authors.affiliation: Brazilian Biosciences National Laboratory, Brazilian Center of Research in Energy and Materials, Rua Giuseppe Máximo Scolfaro, 10.000, Campinas, SP CEP 13083-970, Brazil; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil. Electronic address: lara.peres@lnbio.cnpem.br.
authors.forename: Lara Maldanis Cerqueira
authors.initials: LM
authors.lastname: Peres
authors.affiliation: Brazilian Biosciences National Laboratory, Brazilian Center of Research in Energy and Materials, Rua Giuseppe Máximo Scolfaro, 10.000, Campinas, SP CEP 13083-970, Brazil; Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil. Electronic address: barbara.silva@lnbio.cnpem.br.
authors.forename: Bárbara Santos Pires
authors.initials: BS
authors.lastname: da Silva
authors.affiliation: Brazilian Biosciences National Laboratory, Brazilian Center of Research in Energy and Materials, Rua Giuseppe Máximo Scolfaro, 10.000, Campinas, SP CEP 13083-970, Brazil. Electronic address: luana.santos@lnbio.cnpem.br.
authors.forename: Luana Nunes
authors.initials: LN
authors.lastname: Santos
authors.affiliation: Department of Pharmacology & Toxicology, School of Pharmacy, University of KS, USA. Electronic address: alexmoise@ku.edu.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Moise
authors.affiliation: Brazilian Biosciences National Laboratory, Brazilian Center of Research in Energy and Materials, Rua Giuseppe Máximo Scolfaro, 10.000, Campinas, SP CEP 13083-970, Brazil. Electronic address: hozana.castillo@lnbio.cnpem.br.
authors.forename: Hozana Andrade
authors.initials: HA
authors.lastname: Castillo
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D005075:Biological Evolution; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000187:drug effects / Q000196:embryology* / Q000254:growth & development; D006801:Humans; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D018168:Receptors, Retinoic Acid; D014212:Tretinoin
keywords: ALDH1A2; Heart development; RAR; RXR; Retinoic acid