Subdivision of the Cardiac Nkx2.5 Expression Domain into Myogenic and Nonmyogenic Compartments

Abstract

Nkx2.5 is expressed in the cardiogenic mesoderm of avian, mouse, and amphibian embryos. To understand how various cardiac fates within this domain are apportioned, we fate mapped the mesodermal XNkx2.5 domain of neural tube stage Xenopus embryos. The lateral portions of the XNkx2.5 expression domain in the neural tube stage embryo (stage 22) form the dorsal mesocardium and roof of the pericardial cavity while the intervening ventral region closes to form the myocardial tube. XNkx2.5 expression is maintained throughout the period of heart tube morphogenesis and differentiation of myocardial, mesocardial, and pericardial tissues. A series of microsurgical experiments showed that myocardial differentiation in the lateral portion of the field is suppressed during normal development by signals from the prospective myocardium and by tissues located more dorsally in the embryo, in particular the neural tube. These signals combine to block myogenesis downstream of XNkx2.5 and at or above the level of contractile protein gene expression. We propose that the entire XNkx2.5/heart field is transiently specified as cardiomyogenic. Suppression of this program redirects lateral cells to adopt dorsal mesocardial and dorsal pericardial fates and subdivides the field into distinct myogenic and nonmyogenic compartments.

Perfluoroheptanoic acid affects amphibian embryogenesis by inducing the phosphorylation of ERK and JNK

“…3B and C). NKX2.5 is critical for vasculogenesis and angiogenesis (27). We also assessed the mRNA levels of an intestinal marker, Cyl18, which is mainly expressed in the presumptive small intestine of embryos at the tailbud stage.…”

Geometric Control of Cardiomyogenic Induction in Human Pluripotent Stem Cells

“…Inductive cues originate from the anterior primitive endoderm (Sugi and Lough 1994;Schultheiss, Xydas et al 1995;Schultheiss, Burch et al 1997;Schultheiss and Lassar 1997) and lateral regions of the embryo (Schultheiss, Xydas et al 1995;Schultheiss, Burch et al 1997;Schultheiss and Lassar 1997), while cardiogenesis is suppressed in the adjacent mesoderm by factors secreted by the neuronal tube (Climent, Sarasa et al 1995;Schultheiss, Burch et al 1997;Raffin, Leong et al 2000). Members of the TGF-β superfamily (TGF-β, nodal, activin and BMP) and the FGF family are known cardiogenic morphogens that activate cardiac transcription factors ).…”

“…In the embryo it is recognized that cardiogenesis is directed via the coordination of inductive cues from the anterior primitive endoderm (Sugi and Lough 1994;Schultheiss, Xydas et al 1995;Sugi and Lough 1995;Schultheiss, Burch et al 1997;Schultheiss and Lassar 1997) and inhibitory cues originating from neurogenic tissue (Climent, Sarasa et al 1995;Schultheiss, Burch et al 1997;Raffin, Leong et al 2000). Accordingly, methods to drive mesoderm and cardiac induction during hESC differentiation have included co-culturing hESCs with the visceral endoderm-like cell line END-2 (Mummery, Ward-van Oostwaard et al 2003) or the addition of Transforming Growth Factor Beta (TGF-β) family proteins (most commonly activin A and Bone Morphogenetic Protein (BMP)-2 or BMP-4) that are known to be secreted by primitive endoderm (Burridge, Anderson et al 2007;Laflamme, Chen et al 2007).…”

Inhibition of Wnt activity induces heart formation from posterior mesoderm

“…5B), and the neural plate was considerably expanded in some embryos implanted with Wnt-1 or Wnt-3a pellets (data not shown). Therefore, it was unclear whether repression of Nkx-2.5 gene expression by Wnt signals reflected a direct effect on precardiac mesoderm or a secondary effect because of the expansion of the neural plate, which is known to express inhibitors of cardiogenesis (Jacobson 1960;Climent et al 1995;Raffin et al 2000).…”

“…The neural plate/neural tube has long been known to inhibit cardiogenesis (Jacobson 1960;Climent et al 1995;Raffin et al 2000;Tzahor and Lassar 2001). This laboratory has observed that presumptive head mesoderm from stage 8 embryos, when removed from the adjacent inhibitory influence of neural tube, spontaneously differentiates to heart muscle when cultured with foregut endoderm and the overlying nonneural ectoderm (Tzahor and Lassar 2001).…”