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Heparan sulfate proteoglycans (HSPGs) have long been implicated in a wide range of cell-cell signaling and cell-matrix interactions, both in vitro and in vivo in invertebrate models. Although many of the genes that encode HSPG core proteins and the biosynthetic enzymes that generate and modify HSPG sugar chains have not yet been analyzed by genetics in vertebrates, recent studies have shown that HSPGs do indeed mediate a wide range of functions in early vertebrate development, for example during left-right patterning and in cardiovascular and neural development. Here, we provide a comprehensive overview of the various roles of HSPGs in these systems and explore the concept of an instructive heparan sulfate sugar code for modulating vertebrate development., (© 2015. Published by The Company of Biologists Ltd.)

The secreted TGFbeta factor Lefty antagonizes Nodal signaling during vertebrate embryogenesis, but how it does so has been a mystery. Recent analyses have elucidated the molecular mechanisms underlying this function of Lefty.

How left right handedness originates in the body plan of the developing vertebrate embryo is a subject of considerable debate. In mice, a left right bias is thought to arise from a directional extracellular flow (nodal flow) that is generated by dynein-dependent rotation of monocilia on the ventral surface of the embryonic node. Here we show that the existence of node monocilia and the expression of a dynein gene that is implicated in ciliary function are conserved across a wide range of vertebrate classes, indicating that a similar ciliary mechanism may underlie the establishment of handedness in all vertebrates.

Xenopus and zebrafish serve as outstanding models in which to study vertebrate heart development. The embryos are transparent, allowing observation during organogenesis; they can be obtained in large numbers; and they are readily accessible to embryologic manipulation and microinjection of RNA, DNA, or protein. These embryos can live by diffusion for several days, allowing analysis of mutants or experimental treatments that perturb normal heart development. Xenopus embryos have been used to understand the induction of the cardiac field, the role of Nkx genes in cardiac development, and the role transforming growth factor beta molecules in the establishment and signaling of left-right axis information. Large-scale mutant screens in zebrafish and the development of transgenics in both Xenopus and zebrafish have accelerated the molecular identification of genes that regulate conserved steps in cardiovascular development.

Patterning of all tissues and organs in the vertebrate embryo occurs along the dorsoventral (DV), anteroposterior (AP), and left-right (LR) body axes. Whereas significant progress has been made in identifying the processes underlying DV and AP patterning, relatively little is known about mechanisms guiding LR development. The significant incidence of human disease conditions associated with LR laterality defects, particularly those of the cardiovascular system, underscores the importance of understanding how LR asymmetries become established in the embryo. The focus of this review is on recently identified genes that are involved in generation of vertebrate LR asymmetry, and the proposed cellular and molecular mechanisms by which they might function in initiation, propagation and interpretation of LR patterning information.

The vertebrate body is organized along three geometric axes: anterior-posterior, dorsal-ventral and left-right. Left-right axis formation, displayed in heart and gut development, is the least understood, even though it has been studied for many years. In Xenopus laevis gastrulae, a fibronectin-rich extracellular matrix is deposited on the basal surface of ectoderm cells over which cardiac and visceral primordia move during development. Here I report experiments in which localized perturbation of a small patch of extracellular matrix by microsurgery was correlated with localized randomization of left-right asymmetries. Global perturbation of the extracellular matrix by microinjection of Arg-Gly-Asp peptides or heparinase into the blastocoel resulted in global randomization of left-right asymmetries. From these observations, I suggest that left-right axial information is contained in the extracellular matrix early in development and is independently transmitted to cardiac and visceral primordia.