Talk:Cardiovascular System Development
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Cite this page: Hill, M.A. (2020, October 20) Embryology Cardiovascular System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Cardiovascular_System_Development
Maternal genome-wide DNA methylation patterns and congenital heart defects
PLoS One. 2011 Jan 24;6(1):e16506.
Chowdhury S, Erickson SW, Macleod SL, Cleves MA, Hu P, Karim MA, Hobbs CA. Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas, United States of America.
The majority of congenital heart defects (CHDs) are thought to result from the interaction between multiple genetic, epigenetic, environmental, and lifestyle factors. Epigenetic mechanisms are attractive targets in the study of complex diseases because they may be altered by environmental factors and dietary interventions. We conducted a population based, case-control study of genome-wide maternal DNA methylation to determine if alterations in gene-specific methylation were associated with CHDs. Using the Illumina Infinium Human Methylation27 BeadChip, we assessed maternal gene-specific methylation in over 27,000 CpG sites from DNA isolated from peripheral blood lymphocytes. Our study sample included 180 mothers with non-syndromic CHD-affected pregnancies (cases) and 187 mothers with unaffected pregnancies (controls). Using a multi-factorial statistical model, we observed differential methylation between cases and controls at multiple CpG sites, although no CpG site reached the most stringent level of genome-wide statistical significance. The majority of differentially methylated CpG sites were hypermethylated in cases and located within CpG islands. Gene Set Enrichment Analysis (GSEA) revealed that the genes of interest were enriched in multiple biological processes involved in fetal development. Associations with canonical pathways previously shown to be involved in fetal organogenesis were also observed. We present preliminary evidence that alterations in maternal DNA methylation may be associated with CHDs. Our results suggest that further studies involving maternal epigenetic patterns and CHDs are warranted. Multiple candidate processes and pathways for future study have been identified.
PMID: 21297937 http://www.ncbi.nlm.nih.gov/pubmed/21297937
An endocardial pathway involving Tbx5, Gata4, and Nos3 required for atrial septum formation
Proc Natl Acad Sci U S A. 2010 Oct 25. [Epub ahead of print]
Nadeau M, Georges RO, Laforest B, Yamak A, Lefebvre C, Beauregard J, Paradis P, Bruneau BG, Andelfinger G, Nemer M.
Research Unit in Cardiac Growth and Differentiation and Molecular Biology Program, Université de Montréal, Montréal, QC, Canada H3C 3J7.
Abstract In humans, septal defects are among the most prevalent congenital heart diseases, but their cellular and molecular origins are not fully understood. We report that transcription factor Tbx5 is present in a subpopulation of endocardial cells and that its deletion therein results in fully penetrant, dose-dependent atrial septal defects in mice. Increased apoptosis of endocardial cells lacking Tbx5, as well as neighboring TBX5-positive myocardial cells of the atrial septum through activation of endocardial NOS (Nos3), is the underlying mechanism of disease. Compound Tbx5 and Nos3 haploinsufficiency in mice worsens the cardiac phenotype. The data identify a pathway for endocardial cell survival and unravel a cell-autonomous role for Tbx5 therein. The finding that Nos3, a gene regulated by many congenital heart disease risk factors including stress and diabetes, interacts genetically with Tbx5 provides a molecular framework to understand gene-environment interaction in the setting of human birth defects.
PMID: 20974940 http://www.ncbi.nlm.nih.gov/pubmed/20974940
Heart Valve Development
Transcriptional Regulation of Heart Valve Progenitor Cells
PEDIATRIC CARDIOLOGY Volume 31, Number 3, 414-421, DOI: 10.1007/s00246-009-9616-x
"The development and normal function of the heart valves requires complex interactions among signaling molecules, transcription factors and structural proteins that are tightly regulated in time and space. Here we review the roles of critical transcription factors that are required for specific aspects of normal valve development. The early progenitors of the heart valves are localized in endocardial cushions that express transcription factors characteristic of mesenchyme, including Twist1, Tbx20, Msx1 and Msx2. As the valve leaflets mature, they are composed of complex stratified extracellular matrix proteins that are regulated by the transcriptional functions of NFATc1, Sox9, and Scleraxis. Each of these factors has analogous functions in differentiation of related connective tissue lineages. Together, the precise timing and localized functions of specific transcription factors control cell proliferation, differentiation, elongation, and remodeling processes that are necessary for normal valve structure and function. In addition, there is increasing evidence that these same transcription factors contribute to congenital, as well as degenerative, valve disease."
Regulation of heart valve morphogenesis by Eph receptor ligand, ephrin-A1
Wnt signaling in heart valve development and osteogenic gene induction
Alfieri CM, Cheek J, Chakraborty S, Yutzey KE. Dev Biol. 2010 Feb 15;338(2):127-35. Epub 2009 Dec 1. PMID: 19961844
Heart valve development: regulatory networks in development and disease. Combs MD, Yutzey KE. Circ Res. 2009 Aug 28;105(5):408-21. Review. PMID: 19713546
A new role for the human placenta as a hematopoietic site throughout gestation.
We investigated whether the human placenta contributes to embryonic and fetal hematopoietic development. Two cell populations--CD34(++)CD45(low) and CD34( +)CD45(low)--were found in chorionic villi. CD34(++) CD45(low) cells display many markers that are characteristic of multipotent primitive hematopoietic progenitors and hematopoietic stem cells. Clonogenic in vitro assays showed that CD34(++)CD45( low) cells contained colony-forming units-culture with myeloid and erythroid potential and differentiated into CD56(+) natural killer cells and CD19(+) B cells in culture. CD34(+)CD45(low) cells were mostly enriched in erythroid- and myeloid-committed progenitors. While the number of CD34(++)CD45(low) cells increased throughout gestation in parallel with placental mass. However, their density (cells per gram of tissue) reached its peak at 5 to 8 weeks, decreasing more than 7-fold from the ninth week onward. In addition to multipotent progenitors, the placenta contained intermediate progenitors, indicative of active hematopoiesis. Together, these data suggest that the human placenta is potentially an important hematopoietic organ, opening the possibility of banking placental hematopoietic stem cells along with cord blood for transplantation.
- Endothelial cell lineages of the heart. Ishii Y, Langberg J, Rosborough K, Mikawa T. Cell Tissue Res. 2009 Jan;335(1):67-73. Epub 2008 Aug 6. Review. PMID: 18682987 | PMC: 2729171
The links in this next sections are to the original 2008 online notes pages for Cardiovascular System Development.
Cardiovascular Notes Introduction | Abnormalities | Stage 13/14 | Stage 22 | Stage 22 Selected Highpower | Heart | Heart Rate | BloodBlood Vessels | Molecular | Lymphatic | Text only page | WWW Links | Postnatal | History - Harvey
- Origin, fate, and function of epicardium-derived cells (EPDCs) in normal and abnormal cardiac development. Lie-Venema H, van den Akker NM, Bax NA, Winter EM, Maas S, Kekarainen T, Hoeben RC, deRuiter MC, Poelmann RE, Gittenberger-de Groot AC. ScientificWorldJournal. 2007 Nov 12;7:1777-98. Review. PMID: 18040540 | PDF full article
- Cellular and molecular mechanisms of coronary vessel development. Mu H, Ohashi R, Lin P, Yao Q, Chen C. Vasc Med. 2005 Feb;10(1):37-44. Review. PMID: 15920999
- Development of innervation of coronary arteries in human foetus up until 230 mm. stage (mid-term). Br Heart J. 1970 Jan;32(1):108-13.
- Innervation of the coronary vessels is initiated before the 30mm. stage of development.
- All the main branches of the coronary arteries are formed and in their definitive positions by the 40 mm. stage.
- Two plexuses have been shown for all the larger vessels after the 120 mm. stage.
- There are coarse-fibre and fine-fibre plexuses, situated at different levels in the tunica adventitia.
- Ganglion cells have been found in relation to the coronary arteries over the ventricles.
- This confirms the part played by the vagal system in the innervation of the ventricle.
- No nerve endings were seen in the tunica media.