
Research Summary:
Tissues and organs form during mammalian embryonic development through the integration of numerous signaling and transcriptional pathways. Our major goal is to define pathways controlling organ formation to understand normal development, the molecular basis for congenital defects, and potential mechanisms for organ regeneration and repair. We use a combination of gene knockouts, transgenic reporter assays, biochemical, computational, and genomic approaches to investigate basic developmental mechanisms. We primarily use the mouse as a model system, but several current projects also use cultured cells or zebrafish as models to understand developmental gene regulation. Current work in the lab is focused primarily on cell autonomous mechanisms underlying gene regulation, tissue specification, organ formation and metabolic control during cardiovascular, craniofacial, and neural crest development.
Publications
MEF2C controls segment-specific gene regulatory networks that direct heart tube morphogenesis.
Heart tube morphogenesis is regulated by segment-specific gene regulatory networks controlled by MEF2C.
Zfp106 binds to G-quadruplex RNAs and inhibits RAN translation and formation of RNA foci caused by G4C2 repeats.
ETV2 primes hematoendothelial gene enhancers prior to hematoendothelial fate commitment.
A Mesp1-dependent developmental breakpoint in transcriptional and epigenomic specification of early cardiac precursors.
TCF7L1 Exacerbates Abdominal Aortic Aneurysm Prevalence and Severity.
An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.
Cold shock domain-containing protein E1 is a posttranscriptional regulator of the LDL receptor.
Transcriptional regulation of vascular smooth muscle cell proliferation, differentiation and senescence: Novel targets for therapy.
Differential Etv2 threshold requirement for endothelial and erythropoietic development.
Comprehensive cell type decomposition of circulating cell-free DNA with CelFiE.
Control of ribosomal protein synthesis by the Microprocessor complex.
ATAC-Seq Reveals an Isl1 Enhancer That Regulates Sinoatrial Node Development and Function.
Genome-Wide Analysis Identifies an Essential Human TBX3 Pacemaker Enhancer.
Loss-of-function variants in myocardin cause congenital megabladder in humans and mice.
Venous endothelin modulates responsiveness of cardiac sympathetic axons to arterial semaphorin.
Cardiovascular development and survival require Mef2c function in the myocardial but not the endothelial lineage.
Genomic analysis of transcriptional networks directing progression of cell states during MGE development.
Cooperative activation of cardiac transcription through myocardin bridging of paired MEF2 sites.
Fast revascularization of the injured area is essential to support zebrafish heart regeneration.
MEF2C regulates outflow tract alignment and transcriptional control of Tdgf1.
Nodal Signaling and Congenital Heart Defects.
Endothelin signaling activates Mef2c expression in the neural crest through a MEF2C-dependent positive-feedback transcriptional pathway.
Identification of novel Fgf enhancers and their role in dental evolution.
Mef2c-F10N enhancer driven β-galactosidase (LacZ) and Cre recombinase mice facilitate analyses of gene function and lineage fate in neural crest cells.
Myocyte enhancer factor 2C function in skeletal muscle is required for normal growth and glucose metabolism in mice.
NFATc1 controls skeletal muscle fiber type and is a negative regulator of MyoD activity.
An arterial-specific enhancer of the human endothelin converting enzyme 1 (ECE1) gene is synergistically activated by Sox17, FoxC2, and Etv2.
Specification of the mouse cardiac conduction system in the absence of Endothelin signaling.
Abstract 327: ETS Factors Regulate the VEGF-Dependent, Arterial-Specific Expression of Dll4.
Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants.
ETS factors regulate Vegf-dependent arterial specification.
Regulation of endothelial and hematopoietic development by the ETS transcription factor Etv2.
Transcription factor pathways and congenital heart disease.
Large-scale discovery of enhancers from human heart tissue.
Vascular endothelial and endocardial progenitors differentiate as cardiomyocytes in the absence of Etsrp/Etv2 function.
ETS-dependent regulation of a distal Gata4 cardiac enhancer.
Etsrp/Etv2 initiates endothelial/endocardial and inhibits myocardial differentiation by two distinct mechanisms in zebrafish embryos.
FGF-dependent regulation of VEGF receptor 2 expression in mice.
The MADS box transcription factor MEF2C regulates melanocyte development and is a direct transcriptional target and partner of SOX10.
Hand2 function in second heart field progenitors is essential for cardiogenesis.
Bmp signaling regulates myocardial differentiation from cardiac progenitors through a MicroRNA-mediated mechanism.
ChIP-Seq identification of weakly conserved heart enhancers.
Direct transcriptional regulation of Gata4 during early endoderm specification is controlled by FoxA2 binding to an intronic enhancer.
Development of the endocardium.
Chapter 9.5 Myocyte Enhancer Factor 2 Transcription Factors in Heart Development and Disease.
An endoderm-specific transcriptional enhancer from the mouse Gata4 gene requires GATA and homeodomain protein-binding sites for function in vivo.
Identification and characterization of novel polymorphisms in the basal promoter of the human transporter, MATE1.
Isl1 is a direct transcriptional target of Forkhead transcription factors in second-heart-field-derived mesoderm.
Maintenance of blastemal proliferation by functionally diverse epidermis in regenerating zebrafish fins.
Transcriptional control of endothelial cell development.
Identification and characterization of proximal promoter polymorphisms in the human concentrative nucleoside transporter 2 (SLC28A2).
Combinatorial regulation of endothelial gene expression by ets and forkhead transcription factors.
BMP4 is required in the anterior heart field and its derivatives for endocardial cushion remodeling, outflow tract septation, and semilunar valve development.
A p38 MAPK-MEF2C pathway regulates B-cell proliferation.
Genetic and functional interaction between transcription factors MEF2C and Dlx5/6 is required for craniofacial development.
GATA4 is a direct transcriptional activator of cyclin D2 and Cdk4 and is required for cardiomyocyte proliferation in anterior heart field-derived myocardium.
Foxn4 directly regulates tbx2b expression and atrioventricular canal formation.
Transcriptional pathways in heart development.
Determinants of myogenic specificity within MyoD are required for noncanonical E box binding.
Transcriptional control of second heart field development.
The transcription factor MEF2C is required for craniofacial development.
The heart's Da Vinci code: a Renaissance at Keystone.
Model systems for the study of heart development and disease.
Transcriptional pathways in second heart field development.
Transcriptional Control of Cardiac Boundary Formation.
Increased susceptibility to isoproterenol-induced cardiac hypertrophy and impaired weight gain in mice lacking the histidine-rich calcium-binding protein.
Pitx2 regulates cardiac left-right asymmetry by patterning second cardiac lineage-derived myocardium.
Required, tissue-specific roles for Fgf8 in outflow tract formation and remodeling.
A single mutation causes a spectrum of cardiovascular defects: the potential role of genetic modifiers, epigenetic influences, and stochastic events in phenotypic variability.
The right ventricle, outflow tract, and ventricular septum comprise a restricted expression domain within the secondary/anterior heart field.
Gata4 expression in lateral mesoderm is downstream of BMP4 and is activated directly by Forkhead and GATA transcription factors through a distal enhancer element.
Transgenic mice that express Cre recombinase under control of a skeletal muscle-specific promoter from mef2c.
Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.
Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development.
Mef2c is activated directly by Ets transcription factors through an evolutionarily conserved endothelial cell-specific enhancer.
Mef2c is a direct transcriptional target of ISL1 and GATA factors in the anterior heart field during mouse embryonic development.
HRC is a direct transcriptional target of MEF2 during cardiac, skeletal, and arterial smooth muscle development in vivo.
mef2c is activated directly by myogenic basic helix-loop-helix proteins during skeletal muscle development in vivo.
Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor.
N-twist, an evolutionarily conserved bHLH protein expressed in the developing CNS, functions as a transcriptional inhibitor.
TGF-beta inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3.
Activated notch inhibits myogenic activity of the MADS-Box transcription factor myocyte enhancer factor 2C.
The myogenic regulatory gene Mef2 is a direct target for transcriptional activation by Twist during Drosophila myogenesis.
Multiple roles for the MyoD basic region in transmission of transcriptional activation signals and interaction with MEF2.
Transcriptional control of muscle development by myocyte enhancer factor-2 (MEF2) proteins.
The MEF2A 3' untranslated region functions as a cis-acting translational repressor.
Cooperative transcriptional activation by the neurogenic basic helix-loop-helix protein MASH1 and members of the myocyte enhancer factor-2 (MEF2) family.
MEF2B is a potent transactivator expressed in early myogenic lineages.
Mutational analysis of the DNA binding, dimerization, and transcriptional activation domains of MEF2C.
The mouse MRF4 promoter is trans-activated directly and indirectly by muscle-specific transcription factors.
Effect of vesicular stomatitis virus matrix protein on host-directed translation in vivo.
The role of vesicular stomatitis virus matrix protein in inhibition of host-directed gene expression is genetically separable from its function in virus assembly.
Lack of efficacy of the adenosine reuptake inhibitor dipyridamole in the treatment of anxiety disorders.
Vesicular stomatitis virus matrix protein inhibits host cell-directed transcription of target genes in vivo.
Focal toxicity of oxysterols in vascular smooth muscle cell culture. A model of the atherosclerotic core region.
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