Posts Tagged: cardiac development

Cardiac Regeneration: Lessons From Development

 

Cardiac Regeneration: Lessons From Development

Francisco X. Galdos, Yuxuan Guo, Sharon L. Paige, Nathan J. VanDusen, Sean M. Wu, William T. Pu

Model of the trabeculation process. During trabeulation, a small fraction of cardiomyocytes (CMs) in the compact myocardium (pink) are first specified as trabeculating CMs (brown). These cells delaminate from the compact myocardium and migrate inward to form the first trabecular CMs. CMs in both compacted and trabecular myocardium further proliferate. This proliferation, together with CM migration and rearrangement, results in protrusion and expansion of the trabecular myocardium (illustration credit: Ben Smith). [Powerpoint File]

Cardiac Regeneration: Lessons From Development

Cardiac Regeneration: Lessons From Development

Francisco X. Galdos, Yuxuan Guo, Sharon L. Paige, Nathan J. VanDusen, Sean M. Wu, William T. Pu

Regulation of cardiac progenitor proliferation and differentiation. A, Schematic showing the anterolateral position of first heart field (FHF) progenitors and dorsomedial position of second heart field (SHF) progenitors at embryonic day (E) 7.5. Canonical wingless-type MMTV integration site family member (WNTs), Sonic Hedgehog (SHH), and fibroblast growth factors (FGFs) are expressed dorsally in the region encompassed by the SHF, whereas noncanonical WNTs, BMP2, and FGF8 are expressed ventrally, where the FHF is present. FHF progenitors make up the cardiac crescent and differentiate before the SHF to form the developing heart tube at E8.0. SHF maintains their proliferative state and elongate the heart tube by migrating and differentiating at the inflow and outflow poles of the heart. B, Noncanonical WNTs, BMP2/4, and FGF8 signaling drives FHF progenitors to differentiates toward the myocyte lineage. Meanwhile, canonical WNT/β-catenin, SHH, and FGFs maintain SHF progenitor proliferation. SHF progenitor migration to the outflow and inflow poles of the heart tube exposes them to BMP2/4 and noncanonical WNTs, which drives SHF progenitors to exit their proliferative state and differentiate. C, Canonical WNT/ β-catenin signaling inhibits the differentiation of cardiac progenitors to the myocytes. BMP signaling activates SMAD4 that binds to the transcription factor HOPX to directly inhibit canonical WNT/β-catenin. Moreover, noncanonical WNTs such as WNT5a and WNT11 also inhibit canonical WNT/β-catenin to drive cardiac progenitor differentiation (illustration credit: Ben Smith). [Powerpoint File]

Cardiac Regeneration: Lessons From Development

Cardiac Regeneration: Lessons From Development

Francisco X. Galdos, Yuxuan Guo, Sharon L. Paige, Nathan J. VanDusen, Sean M. Wu, William T. Pu

Specification of mesodermal precursors. Schematic representing the signaling events leading to mesodermal specification during early development. NODAL (nodal growth differentiation factor) is first expressed proximally at embryonic day (E) 5.0. Through an autoregulatory loop, NODAL activates its own expression throughout the epiblast (shown in light purple) and goes on to induce the expression of NODAL antagonists, LEFTY1 and CER1, in the distal visceral endoderm at E5.5 (DVE). The DVE migrates anteriorly where it specifies the anterior portion of the embryo as shown in the yellow hues at E6.5 to 7.5. The anterior visceral endoderm (AVE, yellow) limits NODAL signaling to the posterior of the embryo. Along with wingless-type MMTV integration site family member 3 (WNT3) and bone morphogenic protein (BMP) signaling, NODAL specifies early primitive streak progenitors to the mesoderm fate. [Powerpoint File]

The Ubiquitin-Like SUMO System and Heart Function: From Development to Disease

The Ubiquitin-Like SUMO System and Heart Function: From Development to Disease

Luca Mendler, Thomas Braun, Stefan Müller

Pathway of small ubiquitin-like modifier (SUMO) conjugation/deconjugation and the SUMO-dependent recruitment of SUMO interacting motif (SIM)–containing interaction partners. SUMO is covalently attached to specific lysine (Lys) residues of target proteins in an enzymatic process that involves an E1 activating enzyme (SAE1/SAE2), a single E2 conjugating enzyme (Ubc9), and different SUMO E3 ligases, such as Protein inhibitors of activated STATs (PIAS) proteins, ras-related nuclear protein (Ran)–binding protein 2 (RanBP2), and possibly others. As a result, an isopeptide bond is formed between the C-terminal glycine residues of SUMO and an ε-amino group of a Lys residue of the target protein. Attachment of additional SUMO moieties to internal Lys residues of SUMO induces polymeric chains (mainly by SUMO2/3). SUMO is deconjugated from target proteins by SUMO-specific isopeptidases (SUMO/sentrin-specific protease [SENP]). SUMO conjugates are specifically recognized by interaction partners that possess a specific binding module termed SIM (SUMO interaction motif). SAE1/2 indicates SUMO activating enzyme 1 and 2. [Powerpoint File]

Developmental and Regenerative Biology of Multipotent Cardiovascular Progenitor Cells

Developmental and Regenerative Biology of Multipotent Cardiovascular Progenitor Cells

Anthony C. Sturzu, Sean M. Wu

Proposed cellular hierarchy of cardiac progenitor cells and their lineage diversification. Precursors for heart-forming cells in the vertebrate mesoderm transition from expressing brachyury T to Mesp1 when they enter the precardiac mesoderm stage of development. As these early cardiac mesodermal cells contribute to the developing heart, their transcriptional program determines their further lineage specification. Within the second heart field, Isl1, together with Nkx2.5 and Flk1, defines multipotent Isl1+ cardiovascular progenitor cells that can give rise to myocardial, conduction system, smooth muscle, and endothelial lineages. A subset of precursors derived from Isl1+ progenitors may function as more restricted bipotent progenitors, displaying myocardial and smooth muscle potential or endothelial and smooth muscle potential. The developmental potential of the first heart field progenitors is largely uncharacterized. Epicardial progenitor cells are marked by Wt1 and/or Tbx18. These cells have been shown to give rise to cardiomyocytes, smooth muscle, endothelial cells, and fibroblasts in the heart. CD31 (PECAM 1) indicates platelet/endothelial cell adhesion molecule; cTnT, cardiac troponin T; DDR2, discoidin domain receptor 2; FHF, first heart field; HCN4, potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4; SHF, second heart field; sm-actin, smooth muscle actin; smMHC, smooth muscle myosin heavy chain. (Illustration Credit: Cosmocyte/Ben Smith). [Powerpoint File]

Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells to Cardiomyocytes

Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells to Cardiomyocytes

Christine L. Mummery, Jianhua Zhang, Elizabeth S. Ng, David A. Elliott, Andrew G. Elefanty, Timothy J. Kamp

Model of differentiation of human pluripotent stem cells (hPSC) via sequential progenitors to cardiomyocytes (CMs). On the basis of available data, this simplified model shows the cardiomyocyte lineage hierarchy progressing through sequential progenitors identified by key transcription factors and known cell surface markers. Some of the best characterized signaling pathways responsible for the sequential transitions in cell fate are shown. ESC indicates embryonic stem cell; iPSC, induced pluripotent stem cell; BMP4, bone morphogenetic protein 4; FGF2, fibroblast growth factor 2; SSEA, stage-specific embryonic antigen; EpCAM, epithelial cell adhesion molecule; NCAM, neuronal cell adhesion molecule; KDR, kinase insert domain receptor; PDGFR, platelet-derived growth factor receptor; SIRPA, signal regulatory protein-α; VCAM, vascular cell adhesion molecule. (Illustration: Cosmocyte/Ben Smith.) [Powerpoint File]

Neuregulin in Cardiovascular Development and Disease

Neuregulin in Cardiovascular Development and Disease

Oghenerukevwe Odiete, Michael F. Hill, Douglas B. Sawyer

Biological and physiological role of neuregulin-1 signaling in adult heart. Tissue activities known to be regulated by NRG-1/ErbB signaling in the adult cardiovascular system are shown. EPC indicates endothelial progenitor cell. [Powerpoint File]

Iroquois Homeodomain Transcription Factors in Heart Development and Function

Iroquois Homeodomain Transcription Factors in Heart Development and Function

Kyoung-Han Kim, Anna Rosen, Benoit G. Bruneau, Chi-chung Hui, Peter H. Backx

Irx TF expression in the heart. Schematic illustration of Irx TF expression in the developing and adult hearts. [Powerpoint File]

Cardiopoietic Factors: Extracellular Signals for Cardiac Lineage Commitment

Cardiopoietic Factors: Extracellular Signals for Cardiac Lineage Commitment

Michela Noseda, Tessa Peterkin, Filipa C. Simões, Roger Patient, Michael D. Schneider

Signals for cardiac muscle creation during embryogenesis and stem cell differentiation. Solid and dashed lines indicate positive and negative signals, respectively, at the indicated developmental stages. Circular arrows denote self-renewal. Timing relative to Mesp1 is inferred in some instances, eg, by the presence of mesoderm derivatives known to require Mesp genes. [Powerpoint File]

Zebrafish in the Study of Early Cardiac Development

Zebrafish in the Study of Early Cardiac Development

Jiandong Liu, Didier Y.R. Stainier

RA signaling restricts cardiogenic potential. A, nkx2.5 and cmlc2 expression domains are expanded in aldh1a2 (also known as neckless) mutant embryos compared with wild-type (6-somite stage for nkx2.5 expression and 16-somite stage for cmlc2 expression). Dorsal views, anterior to the top. B through D, Construction of blastomere fate map with caged fluorescein. B, Lateral view of 2 neighboring blastomeres (40% epiboly stage) in tier 3 that were labeled by activating caged fluorescein. C, Animal pole view of labeled blastomeres (arrowhead). The dorsal midline was labeled by Tg (gsc:GFP) expression (arrow). D, Descendants of the labeled blastomeres were identified in the heart (arrows, 44 hours after fertilization). E and F, Schematics illustrate that more blastomeres have cardiogenic potential in BMS189453-treated embryos than in control (40% epiboly blastula stage). Adapted from Keegan BR, et al, Science. 2005;307:247–249. [Powerpoint File]