The role of nuclear receptors in the atrial specification

• Grant number: 11/15273-7
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): May 01, 2012
• Effective date (End): April 30, 2014
• Field of knowledge: Biological Sciences - Morphology - Embryology
• Principal Investigator: José Xavier Neto
• Grantee: Bárbara Santos Pires da Silva
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil

Abstract

The vertebrate heart develops initially as a cardiac tube that undergoes molecular patterning processes along the anteroposterior axis (AP) to form the regions that will give rise to the future cardiac chambers. This patterning process results in the emergence of inflow chambers, such as atrium and venous sinus in the posterior region of the heart and the ventricles and outflow tract in the anterior region. The establishment of the AP axis with the appropriate topology is essential to effectively articulate the heart with the circulation, so that the inflow chambers receive venous blood and outflow chambers, or ventricles, dump their output into the aorta through an outflow tract.Multiple signaling molecules may be involved in cardiac AP patterning and retinoic acid (RA) is an excellent candidate for this process. The RA is an essential molecule for growth and development. During early embryonic development the RA signaling is often related to the establishment of a posterior character to the structures in which it is activated.The patterning processes that give the posterior identity to the cardiac chambers due to RA signaling can be examined through the expression of molecular markers. A few years ago we described an excellent marker of this process, the gene for slow myosin heavy chain SMyHC3 of quail (Coturnix japonica). The promoter of this gene contains a 5' region of 160pb between -840 and-680pb, called atrial regulatory domain 1 (ARD1) that acts as an atrial-specific enhancer in cultured cardiomyocytes and in embryos. The main objective of this project is to identify the transcription factors that regulate the SMyHC3 promoter. The cardiac patterning process, and besides being regulated by RA also appears to be regulated by genes such as the orphan nuclear receptor COUP-TFII, which controls biological processes such as angiogenesis, cardiac and neural development. According to earlier studies done by our group, the hypothesis that guides this project is that the RA acts indirectly through COUPTF-II, to activate atrial specification and, consequently, activate the SMyHC3 promoter. (AU)

Scientific publications

(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; SOUSA COSTA, ANGELA M.; FIGUEIRA, ANA CAROLINA M.; CAIAFFA, CARLO DONATO; DO AMARAL, FABIO NEVES; CERQUEIRA PERES, LARA MALDANIS; PIRES DA SILVA, BARBARA SANTOS; SANTOS, LUANA NUNES; MOISE, ALEXANDER R.; CASTILO, HOZANA ANDRADE. Signaling through retinoic acid receptors in cardiac development: Doing the right things at the right times. BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, v. 1849, n. 2, SI, p. 94-111, FEB 2015. (12/14859-0, 13/12008-6, 11/15273-7)

XAVIER-NETO, JOSE; SOUSA COSTA, ANGELA M.; FIGUEIRA, ANA CAROLINA M.; CAIAFFA, CARLO DONATO; DO AMARAL, FABIO NEVES; CERQUEIRA PERES, LARA MALDANIS; PIRES DA SILVA, BARBARA SANTOS; SANTOS, LUANA NUNES; MOISE, ALEXANDER R.; CASTILO, HOZANA ANDRADE. Signaling through retinoic acid receptors in cardiac development: Doing the right things at the right times. BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS, v. 1849, n. 2, p. 18-pg., 2015-02-01. (11/15273-7, 13/12008-6, 12/14859-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SILVA, Bárbara Santos Pires da. The role of nuclear receptors in atrial specification.. 2014. Master's Dissertation - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.