Extracellular matrix of the developing heart in normal and cardiac lethal mutant axolotls, Ambystoma mexicanum

Abstract

As part of an ongoing study of heart development in normal and cardiac lethal mutant axolotls (Mexican salamanders) we examined the extracellular matrix (ECM) by microscopical methods. With scanning electron microscopy we are unable to detect ECM on the apical surface of cells of the early cardiogenic mesoderm. During the period of lateral plate migration, which coincides with the period of cardiogenic induction of mesoderm by anterior endoderm, there is little ECM, aside from some microfibrils, on the basal surface of the endoderm or mesoderm of the pharyngeal region. Later, a basal lamina (BL) is found on the endoderm and along portions of the developing endocardial and myocardial tubes. By the time of heartbeat initiation the BLs are complete and invested with striated collagen-like fibrils that are sparsely distributed in the "cardiac jelly" of normal and mutant hearts. Striated fibril deposition, which increases with time, is generally random in orientation, with the exception of some regions where there is a preferred directionality. During the post-hatching period striated fibrils appear in the subepicardial space. In addition, branching fibers that are probably elastin appear in the bulbus arteriosus. In these later stages the density of fibrils in the cardiac lethal mutant heart is much less than normal. Indirect immunofluorescent microscopy reveals laminin and fibronectin in the basal laminae of the endocardial and myocardial tubes of both normal and cardiac lethal mutant hearts. In addition, punctate and fibrillar staining for fibronectin, and punctate staining for laminin are found in the cardiac jelly. These matrix proteins are not abundant at the apical (exterior) surface of the myocardium until the epicardium appears.(ABSTRACT TRUNCATED AT 250 WORDS)

Pleiotropic effects of the Cardiac‐lethal gene in the axolotl (Ambystoma mexicanum)

“…Although Fransen and Lemanski (1991) proposed that these differences are due to hypoxia resulting from the lack of circulation, our results suggest that they are directly caused by the c gene.…”

What Is the Purpose of the Embryonic Heart Beat? or How Facts Can Ultimately Prevail over Physiological Dogma

“…One of the first cardiovascular mutants to receive considerable scrutiny was not in zebra fish or other relatively new animal models but rather in the axolotl Ambystoma mexicanum (Lemanski 1973). The gene c cardiac mutant of this species produces myocardial cells that fail to form organized myofibrils and thus fail to develop a heart beat (see reviews by Fransen and Lemanski 1989;Lemanski et al 1995). Although almost all attention has been on the cardiac electrophysiology, contractility, and ultrastructure of this mutant, buried in the original articles are the observations that the larvae not only hatch and survive but continue to grow and swim around with a nonbeating heart for up to 2 wk.…”

The Lhx9-Integrin pathway is essential for positioning of the proepicardial organ

“…Using a pharmacological small-molecule screen in Xenopus, we ascertained that integrin-paxillin signaling is required for proper PE clustering, which is confirmed by a significant decrease in epicardial integrin alpha 4 (itga4) expression upon loss of Lhx9 function. Given that interactions between cells and the surrounding ECM are vital for epicardial formation and its role in cardiac repair (Kálmán et al, 1995;Nahirney et al, 2003;Pae et al, 2008;Wang et al, 2013;Benesh et al, 2013;Fransen and Lemanski, 1991;Mercer et al, 2013;Rongish et al, 1996;Yang et al, 1995), we further show a novel function for Lhx9 in mediating integrin adhesion mechanisms for correct PE cell clustering. Therefore, Lhx9 is vital for the formation of the epicardium and development of the heart.…”