Abstract

This project aims to uncover signaling molecules that initiate heart formation in the early embryo and limit dorsal spread of heart tissue, and study the possible involvement of the Notch/Delta signalling interaction in limiting the size of the heart.
Aim 1 is to co-culture regions of the blastula known by fate mapping to give rise to the heart together with the endoderm, which is known to induce heart, and use many markers of cardiac development to see what exactly has been induced.
Aim 2 is to take the same cardiogenic regions and overexpress various growth factors artificially in adjacent cells, and ask whether this induces heart.
Aim 3) is to co-culture the lateral and ventral mesoderm of the tailbud stage embryo together with isolated neural tissue, to see if less heart tissue forms.
Aim 4) is to overexpress notch or a domininant-negative form of notch, by injection into blastomeres in the heart-forming region, and see if the amount of heart-forming tissue is altered.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL059502-02
Application #
2750645
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1997-08-01
Project End
2001-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Lanier, Marion; Schade, Dennis; Willems, Erik et al. (2012) Wnt inhibition correlates with human embryonic stem cell cardiomyogenesis: a structure-activity relationship study based on inhibitors for the Wnt response. J Med Chem 55:697-708
Mercola, Mark; Doevendans, Pieter (2012) Meeting review: cardiomyocyte regeneration and protection, La Jolla, California, June 2011. J Cardiovasc Transl Res 5:100-5
McKeithan, Wesley L; Colas, Alexandre R; Bushway, Paul J et al. (2012) Serum-free generation of multipotent mesoderm (Kdr+) progenitor cells in mouse embryonic stem cells for functional genomics screening. Curr Protoc Stem Cell Biol Chapter 1:Unit 1F.13
Willems, Erik; Cabral-Teixeira, Joaquim; Schade, Dennis et al. (2012) Small molecule-mediated TGF-? type II receptor degradation promotes cardiomyogenesis in embryonic stem cells. Cell Stem Cell 11:242-52
Schade, Dennis; Lanier, Marion; Willems, Erik et al. (2012) Synthesis and SAR of b-annulated 1,4-dihydropyridines define cardiomyogenic compounds as novel inhibitors of TGF? signaling. J Med Chem 55:9946-57
Willems, Erik; Spiering, Sean; Davidovics, Herman et al. (2011) Small-molecule inhibitors of the Wnt pathway potently promote cardiomyocytes from human embryonic stem cell-derived mesoderm. Circ Res 109:360-4
Willems, Erik; Lanier, Marion; Forte, Elvira et al. (2011) A chemical biology approach to myocardial regeneration. J Cardiovasc Transl Res 4:340-50
Princen, Frederic; Bard, Emilie; Sheikh, Farah et al. (2009) Deletion of Shp2 tyrosine phosphatase in muscle leads to dilated cardiomyopathy, insulin resistance, and premature death. Mol Cell Biol 29:378-88
Foley, Ann C; Korol, Oksana; Timmer, Anjuli M et al. (2007) Multiple functions of Cerberus cooperate to induce heart downstream of Nodal. Dev Biol 303:57-65
Rutenberg, Joshua B; Fischer, Andreas; Jia, Haibo et al. (2006) Developmental patterning of the cardiac atrioventricular canal by Notch and Hairy-related transcription factors. Development 133:4381-90

Showing the most recent 10 out of 26 publications