Studies on cell differentiation mechanisms during early bovine embryo development

• Grant number: 17/09576-3
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: December 01, 2017
• End date: May 31, 2023
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Marcelo Demarchi Goissis
• Grantee: Marcelo Demarchi Goissis
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: José Antonio Visintin ; Mayra Elena Ortiz D' Avila Assumpcao
• Associated scholarship(s): 22/02748-1 - Effect of mTOR pathway stimulation during embryonic culture in the absence or presence of glucose on trophectoderm differentiation in embryos cattle., BP.MS; 19/21303-8 - Effect of inhibition of fibroblast growth factor receptors in the differentiation of primitive endoderm in bovine embryos produced in vitro, BP.IC; 19/22798-0 - Effect of fibroblast growth factor 4 (FGF4) in the differentiation of primitive endoderm in bovine embryos, BP.IC; + associated scholarships 19/22649-5 - Functional evaluation of NANOG gene in segregation of cell lineages in bovine embryos, BP.MS; 19/03014-9 - Insertion of fluorescent reporter gene in Sox2 gene region to study cell differentiation in early bovine embryo development, BP.MS; 18/18924-8 - Influence of the HIPPO signaling pathway on the segregation between the inner cell mass and the trophectoderm in bovine embryos, BP.MS; 18/08285-8 - Influence of cell contractility on the formation of apical domains and lineage segregation in the bovine embryo, BP.IC; 17/25574-0 - Studies on cell differentiation mechanisms during early bovine embryo development, BP.JP - associated scholarships

Abstract

The first events of cellular differentiation occur before embryo implantation in mammals. They consist in the segregation between the inner cell mass and the trophectoderm, followed by segregation between epiblast and primitive endoderm within the inner cell mass. This differentiation process involves different molecular mechanisms, from cell polarization to temporally regulated expression of lineage-specific transcription factors. Recent data suggest that pre-implantation bovine embryo development can be a good model for human early development. The aim of this project is to investigate mechanisms related to early lineage segregation during bovine embryo development. We propose experiments to test hypotheses related to the first and second events of embryonic cell differentiation. We intend to assess the influence of cell polarization and Hippo signaling activity during inner cell mass and trophectoderm segregation. Then, the roles of NANOG and GATA6 transcription factors on epiblast and primitive endoderm segregation will be tested. Experimental approaches to be used will include use of small molecule inhibitors, CRISPR/Cas9-mediated gene editing and single-cell global gene expression analysis. This research project will bring a deeper understanding about mechanisms involved on the first differentiation choices of the bovine embryo. A deeper knowledge of these mechanisms will aid understanding issues related to in vitro fertilization, nuclear transfer techniques and pluripotent cell culture. (AU)

Scientific publications

(6)

(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)

DOS ANJOS, S. A. A.; DA COSTA, C. P.; ASSUMPCAO, M. E. O. A.; VISINTIN, J. A.; GOISSIS, M. D.. Inhibition of apical domain formation does not block blastocyst development in bovine embryos. REPRODUCTION FERTILITY AND DEVELOPMENT, JUN 2021. (17/25574-0, 17/09576-3, 18/08285-8, 18/18924-8)

LUEDKE, FELIPE EDUARDO; DA COSTA, CAROLINE PEREIRA; MENDES, CAMILLA MOTA; DOS SANTOS HAMILTON, THAIS ROSE; MILAZZOTTO, MARCELLA PECORA; ASSUMPCAO, MAYRA E. O. A.; GOISSIS, MARCELO DEMARCHI. Effects of fetal bovine serum on trophectoderm and primitive endoderm cell allocation of in vitro-produced bovine embryos. ZYGOTE, v. 31, n. 1, p. 7-pg., 2022-10-24. (18/18924-8, 17/09576-3, 19/03014-9, 17/25574-0)

SANTOS, GABRIEL S.; MARTINS, MATHEUS P.; LUEDKE, FELIPE E.; TANAKA, YUKI; CARREIRO, LETICIA E.; MENDES, CAMILLA MOTA; GOISSIS, MARCELO DEMARCHI. Inhibition of FGF receptor impairs primitive endoderm differentiation in bovine embryos. REPRODUCTION IN DOMESTIC ANIMALS, v. 58, n. 2, p. 9-pg., 2022-11-14. (19/21303-8, 19/22798-0, 17/09576-3)

DOS ANJOS, S. A. A.; DA COSTA, C. P.; ASSUMPCAO, M. E. O. A.; VISINTIN, J. A.; GOISSIS, M. D.. Inhibition of apical domain formation does not block blastocyst development in bovine embryos. REPRODUCTION FERTILITY AND DEVELOPMENT, v. 33, n. 10, p. 665-673, AUG 11 2021. (17/09576-3, 18/08285-8, 18/18924-8, 17/25574-0)

CARREIRO, LETICIA ESCOBAR; DOS SANTOS, GABRIEL SIQUEIRA; LUEDKE, FELIPE EDUARDO; GOISSIS, MARCELO DEMARCHI. ell differentiation events in pre-implantation mouse and bovine embryo. ANIMAL REPRODUCTION, v. 18, n. 4, 2021. (19/22649-5, 19/21303-8, 19/03014-9, 17/09576-3)

LETÍCIA ESCOBAR CARREIRO; GABRIEL SIQUEIRA DOS SANTOS; FELIPE EDUARDO LUEDKE; MARCELO DEMARCHI GOISSIS. Cell differentiation events in pre-implantation mouse and bovine embryos. Animal Reproduction, v. 18, n. 4, 2022-01-07. (19/21303-8, 19/03014-9, 19/22649-5, 17/09576-3)