Development of oligodendrocytes, myelin-forming glia in the central nervous system (CNS), proceeds on a protracted schedule. Specification of oligodendrocyte progenitors (OLPs) begins early in development, whereas their terminal differentiation occurs at late embryonic and postnatal periods. How these distinct steps are controlled remains unclear. Our previous study demonstrated an important ro...

Ventricular septal defect (VSD) is the most common cardiovascular malformation and an important contributor to the substantial morbidity and mortality in infancy. Growing evidence suggests that genetic defects play important roles in the pathogenesis of congenital VSD. However, VSD is of great genetic heterogeneity and the genetic basis for VSD in the majority of the patients remains largely un...

The cardiac conduction system is an anatomically discrete segment of specialized myocardium that initiates and propagates electrical impulses to coordinate myocardial contraction. To define the molecular composition of the mouse ventricular conduction system we used microdissection and transcriptional profiling by serial analysis of gene expression (SAGE). Conduction-system-specific expression ...

Transcription factors (TFs) are thought to function with partners to achieve specificity and precise quantitative outputs. In the developing heart, heterotypic TF interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5, have been proposed as a mechanism for human congenital heart defects. We report extensive and complex interdependent genomic occupancy of TBX5, NKX2-5, and...

PTPN2 is a risk gene for Crohn's disease (CD). We investigated whether PTPN2 genetic variants (rs2542151 and rs2542152) were associated with CD in a familial IBD registry. Both rs2542151 and rs2542152 are associated with CD, but not ulcerative colitis (UC). mRNA expression levels of PTPN2 were significantly increased in intestinal tissues (p=0.0493), and nearly significantly increased in B cell...

The purposes of this study are to investigate somatic NKX2-5 mutations in Chinese children with congenital heart disease (CHD) and assess the reliability of somatic mutation detection in formalin-fixed, paraffin-embedded (FFPE) tissues. The study cohort included frozen and FFPE cardiac tissues as well as blood samples from 85 Chinese children with CHD who had the cardiac operations. The right a...

The clinical importance of anterior foregut endoderm (AFE) derivatives, such as thyrocytes, has led to intense research efforts for their derivation through directed differentiation of pluripotent stem cells (PSCs). Here, we identify transient overexpression of the transcription factor (TF) NKX2-1 as a powerful inductive signal for the robust derivation of thyrocyte-like cells from mouse PSC-de...

To identify the molecular pathways that guide cardiac ventricular chamber specification, maturation and morphogenesis, we have sought to characterize factors that regulate the expression of the ventricular myosin light chain-2 gene, one of the earliest markers of ventricular regionalization during mammalian cardiogenesis. Previously, our laboratory identified a 28 bp HF-la/MEF-2 element in the ...

PURPOSE Foxhead box M1 (FOXM1) expression has been shown to be linked with human papillomavirus (HPV) 16/18-infected cervical cancer. However, the mechanism underlying the induction of FOXM1 in HPV 16/18-infected cancers remains elusive. EXPERIMENTAL DESIGN The mechanistic actions of FOXM1 induced by the E6/NKX2-1 axis in tumor aggressiveness were elucidated in cellular and animal models. The...

PURPOSE Aberrant DNA methylation changes are common somatic alterations in prostate carcinogenesis. We examined the methylation status of six genes in prostate tissue specimens from African American (AA) and Caucasian (Cau) males. EXPERIMENTAL DESIGN We used pyrosequencing to quantitatively measure the methylation status of GSTP1, AR, RARbeta2, SPARC, TIMP3, and NKX2-5. Real-time PCR was used...