Heart induction in salamanders

Abstract

Heart determination is a gradual, cumulative process involving inductive and suppressive interactions between the heart mesoderm and nearby embryonic tissues. Our analysis of heart determination in the California newt, Taricha torosa, includes defect and other i n vivo experiments, and explants in epidermal vesicles and into hanging drops.Explants of presumptive heart mesoderm from neurulae into hanging drops of a completely defined salt solution (Niu-Twitty solution) produce beating hearts only infrequently. The addition of various other tissues and fractions of tissue homogenates changes the frequency and the rate of differentiation. These two parameters were used to assess the stimulatory and suppressive effects of tissues and tissue fractions on the differentiation of the presumptive heart mesoderm.At least three different factors are active in eliciting and regulating heart differentiation. A specific heart inductor in anterior endoderm increases the rate and the frequency of heart differentiation. A general stimulatory factor in epidermis and other embryonic tissues increases the frequency, but not the rate, of heart differentiation. A n inhibitory agent in cranial fold and neural plate tissues delays or prevents heart differentiation. These three factors operate from intact tissues in the embryo or when explanted in vesicles or hanging drops, and are effectively present in a fraction (from sephadex column chromatography) of homogenates of the appropriate tissues.Heart formation in vertebrates is clearly dependent upon a variety of developmental conditions and processes. We shall describe some of these and attempt to integrate them into a unified concept of heart differentiation.By the time an embryo has formed the three germ layers, heart potentialities have become limited to, or have developed only in, specific regions of the mesoderm. Portions of the endoderm and the ectoderm have significant interactions with the mesoderm, and these interactions control heart formation. As with so many organs, the heart is induced.Prospective heart mesoderm has its most important inductive interactions with the anterior dorso-lateral endoderm of the early embryo. This has been experimentally demonstrated in amphibians (Mangold, '56; Chuang and Tseng, '57; Amano, '58; Jacobson, '60, '61), in chicks (Orts-Llorca, '63; Orts-Llorca and Gil, '65), and is implied for human embryos by observations of Hommes ('57).Partly as a result of embryonic induction, areas of mesoderm become determined to form a whole heart. For a time during heart determination, any part of such an area may form a whole heart if isolated from the remainder. This is readily seen if one prevents the fusion of the two groups that normally come together to form a single heart. Each half-rudiment forms a whole heart, one the mirror image of the other (Ekman, '25; Copenhaver, '26, '55; DeHaan, '65).The positions of the cells that are induced to form heart and the morphogenetic movements that bring these cells to the heart site need explanation. Atte...

Precardiac mesoderm is specified during gastrulation in quail

“…Our experiments also cannot rule out a potential inductive role of endoderm prior to stage 4 + . Although this question has been addressed in anurans and urodeles by removing endoderm from successively younger embryos (Nieuwkoop, 1947;Jacobson, 1960Jacobson, ,1961Jacobson and Duncan, 1968;Sater and Jacobson, 1990a), our results concerning the timing of PCM specification and recent fate mapping studies suggest that this approach may not be feasible in birds. Cells destined to form the heart pass through the primitive streak during stage 3a-b (Garcia-Martinez and , approximately coincident with the movement of endodermal cells through the streak and displacement of the hypoblast rostrally.…”

“…In urodeles, endoderm influences heart development first through the initial inductive influence required for the establishment of PCM and subsequently via "formative influences" that increase the degree of heart muscle cell differentiation and heart tube formation (Mangold, 1954(Mangold, , 1956Holtfreter and Hamburger, 1955;Jacobson, 1960Jacobson, ,1961. In Taricha torosa, anterolateral endoderm (and homogenates of endoderm) also increases the rate of heart formation, as assayed by the initiation of heartbeat (Jacobson and Duncan, 1968). Our results show that anterolateral endoderm influences several aspects of heart development in quail.…”

“…A classical view of heart development suggests that mesoderm with the capacity to form heart muscle arises in response to an inductive influence of anterior endoderm (reviewed in Jacobson and Sater, 1988 most compelling evidence for a n inductive role of endoderm is derived from whole embryo and explant studies in several species of urodeles, which have shown that formation of a beating heart is dependent upon an interaction between lateral mesoderm and pharyngeal endoderm during early-to-mid-neurula stages of development (Nieuwkoop, 1947;Chuang and Tseng, 1957;Jacobson, 1960Jacobson, ,1961Jacobson and Duncan, 1968). In the urodele Taricha torosa, precardiac mesoderm (PCM) is not specified (capable of differentiating in isolation from other cell layers) until midneurula stages, since explants of heart forming regions from younger embryos must contain endoderm for beating heart structures to form (Jacobson, 1961).…”

Geometric Control of Cardiomyogenic Induction in Human Pluripotent Stem Cells

“…A number of studies across various species have demonstrated that interactions between endoderm and overlying mesoderm are involved in cardiac differentiation (Orts Llorca 1963;Jacobson and Duncan 1968;Sugi and Lough 1994;Nascone and Mercola 1995;Schultheiss, Xydas et al 1995) and, more specifically, play an inductive role as evidenced by the generation of beating cardiac tissue in cocultures of non-cardiogenic embryonic tissue explants and endodermal tissue (Schultheiss, Xydas et al 1995). The inductive characteristic of the endoderm can be attributed to TGF-β superfamily and FGF family growth factors, expressed by anterior lateral endoderm, that have been reported to be involved in cardiac differentiation.…”

Anterior endoderm is a specific effector of terminal cardiac myocyte differentiation of cells from the embryonic heart forming region

“…Despite this, studies in which anterior (pharyngeal) endoderm was removed or transplanted have provided evidence that these cells have an instructive or permissive role in embryonic cardiogenesis (reviewed by Jacobson and Sater, 1988). For example, in several urodele species, removal of endoderm from neurula-stage embryos has been shown to prevent heart formation (Jacobson, 1960(Jacobson, , 1961Jacobson and Duncan, 1968;Fullilove, 1970). Moreover, normal anterior endoderm has been shown to induce myofibrillogenesis and contractility in pre-cardiac mesoderm explanted from mutant salamanders which exhibit abnormal cardiac development (Lemanski et al, 1979).…”