Okihiro syndrome refers to the association of forearm malformations with Duane syndrome of eye retraction. Based on the reported literature experience, clinical diagnosis of the syndrome can be elusive, owing to the variable presentation in families reported. Specifically, there is overlap of clinical features with other conditions, most notably Holt-Oram syndrome, a condition resulting from mu...

The ventricular conduction system (VCS) orchestrates the harmonious contraction in every heartbeat. Defects in the VCS are often associated with life-threatening arrhythmias and also promote adverse remodeling in heart disease. We have previously established that the Irx3 homeobox gene regulates rapid electrical propagation in the VCS by modulating the transcription of gap junction proteins Cx4...

T-box genes encode putative transcription factors implicated in diverse developmental processes (Papaioannou, V.E. and Silver, L.M., 1998. BioEssays 20, 9-19). We have previously reported the embryonic expression patterns of T-box genes in mice (Chapman, D.L., Garvey, N., Hancock, S., Alexiou, M., Agulnik, S.I., Gibson-Brown, J.J., Cebra-Thomas, J., Bollag, R.J., Silver, L.M., Papaioannou, V.E....

RATIONALE Generation of induced cardiac myocytes (iCMs) directly from fibroblasts offers great opportunities for cardiac disease modeling and cardiac regeneration. A major challenge of iCM generation is the low conversion rate of fibroblasts to fully reprogrammed iCMs, which could in part be attributed to unbalanced expression of reprogramming factors Gata4 (G), Mef2c (M), and Tbx5 (T) using th...

The transition from the single circulation of the embryo to the double circulation of the neonatal and adult heart involves the transformation of the primitive heart tube through a complex morphogenetic process, resulting in completely separated right and left heart chambers and distinct pulmonary and systemic circulations. Septation of heart chambers starts at early stages in embryogenesis and...

Vertebrates have two pairs of morphologically distinct appendages, the forelimbs and the hindlimbs. Although the mechanisms necessary for limb outgrowth and polarity are becoming fairly well-understood little is known about how limb-type identity is regulated. The homeobox containing transcription factor Pitx1 expressed in hindlimb bud mesenchyme and has been shown to be involved in limb-type d...

We analyzed the effect of conditional, alphaMHC-dependent genetic beta-catenin depletion and stabilization on cardiac remodeling following experimental infarct. beta-Catenin depletion significantly improved 4-week survival and left ventricular (LV) function (fractional shortening: CT(Deltaex3-6): 24 +/- 1.9%; beta-cat(Deltaex3-6): 30.2 +/- 1.6%, P < 0.001). beta-Catenin stabilization had opposi...

The multi-chambered mammalian heart arises from a simple tube by polar elongation, myocardial differentiation and morphogenesis. Members of the large family of T-box (Tbx) transcription factors have been identified as crucial players that act in distinct subprogrammes during cardiac regionalization. Tbx1 and Tbx18 ensure elongation of the cardiac tube at the anterior and posterior pole, respect...