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Left-right symmetry breaking is a complex developmental process and an important part of embryonic axis development. As of yet, the biophysical mechanism behind LR asymmetry establishment remains elusive for the overall asymmetry of embryos as well as for the organ-specific asymmetry. Here, we demonstrate that inherent cellular chirality is observable in the cells of early embryonic stages using a 3D Matrigel bilayer system. Differentiation of human embryonic stem cells to three lineages corresponding to heart, intestine, and neural tissues demonstrates phenotype-specific inherent chiral biases, complementing the current knowledge regarding organ development. The existence of inherent cellular chirality early in development and its correlation with organ asymmetry implicate cell chirality as a possible regulator in LR symmetry breaking. [ABSTRACT FROM AUTHOR]

Birth defects are a common occurrence in the United States and worldwide. Currently, evaluation of potential developmental toxicants (i.e., teratogens) relies heavily on animal-based models which do not always adequately mimic human development. In order to address this, researchers are developing in vitro human-based models which utilize human pluripotent stem cells (hPSCs) to assess the teratogenic potential of chemical substances. The field of human developmental toxicity assays includes a variety of platforms including monolayer, micropattern, embryoid body, and 3D organoid cultures. In this review, we will overview the field of human teratogenic assays, detail the most recent advances, and discuss current limitations and future perspectives. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that intrinsic cell chirality significantly contributes to the left-right (LR) asymmetry in embryonic development, which is a well-conserved characteristic of living organisms. With animal embryos, several theories have been established, but there are still controversies regarding mechanisms associated with embryonic LR symmetry breaking and the formation of asymmetric internal organs. Recently, in vitro systems have been developed to determine cell chirality and to recapitulate multicellular chiral morphogenesis on a chip. These studies demonstrate that chirality is indeed a universal property of the cell that can be observed with well-controlled experiments such as micropatterning. In this paper, we discuss the possible benefits of these in vitro systems to research in LR asymmetry, categorize available platforms for single-cell chirality and multicellular chiral morphogenesis, and review mathematical models used for in vitro cell chirality and its applications in in vivo embryonic development. These recent developments enable the interrogation of the intracellular machinery in LR axis establishment and accelerate research in birth defects in laterality.This article is part of the themed issue 'Provocative questions in left-right asymmetry'., (© 2016 The Author(s).)