Polarity and cell division orientation in the cleavage embryo: from worm to human.

Cleavage is a period after fertilization, when a 1-cell embryo starts developing into a multicellular organism. Due to a series of mitotic divisions, the large volume of a fertilized egg is divided into numerous smaller, nucleated cells-blastomeres. Embryos of different phyla divide according to different patterns, but molecular mechanism of these early divisions remains surprisingly conserved. In the present paper, we describe how polarity cues, cytoskeleton and cell-to-cell communication interact with each other to regulate orientation of the early embryonic division planes in model animals such as Caenorhabditis elegans, Drosophila and mouse. We focus particularly on the Par pathway and the actin-driven cytoplasmic flows that accompany it. We also describe a unique interplay between Par proteins and the Hippo pathway in cleavage mammalian embryos. Moreover, we discuss the potential meaning of polarity, cytoplasmic dynamics and cell-to-cell communication as quality biomarkers of human embryos.A.A. is a beneficent of the National Science Centre grant (UMO-2012/07/D/NZ5/04301). M.Z.-G. thanks the Wellcome Trust for supporting the work in her laboratory. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust.This is the final version of the article. It was first available from Oxford University Press via http://dx.doi.org/10.1093/molehr/gav06

Advances in embryo selection methods

Despite many recent advances in the field of reproductive biology and medicine, the efficiency of in vitro fertilization procedures remains relatively low. There is a need for a reliable and non-invasive method of embryo selection to ensure that only embryos with the highest developmental potential are chosen for transfer to mothers-to-be. Here, we compare various methods currently used for assessing embryonic viability, such as examination of embryonic morphology, quality of the genetic material, or metabolism. Additionally, we discuss novel procedures for embryonic assessment based on advanced time-lapse imaging techniques, which show great promise and may lead to increased in vitro fertilization efficiencies

Animal and vegetal poles of the mouse egg predict the polarity of the embryonic axis, yet are nonessential for development

Recent studies suggest early (preimplantation) events might be important in the development of polarity in mammalian embryos. We report here lineage tracing experiments with green fluorescent protein showing that cells located either near to or opposite the polar body at the 8-cell stage of the mouse embryo retain their same relative positions in the blastocyst. Thus they come to lie on either end of an axis of symmetry of the blastocyst that has recently been shown to correlate with the anterior-posterior axis of the postimplantation embryo (see R. J. Weber, R. A. Pedersen, F. Wianny, M. J. Evans and M. Zernicka-Goetz (1999). Development 126, 5591-5598). The embryonic axes of the mouse can therefore be related to the position of the polar body at the 8-cell stage, and by implication, to the animal-vegetal axis of the zygote. However, we also show that chimeric embryos constructed from 2-cell stage blastomeres from which the animal or the vegetal poles have been removed can develop into normal blastocysts and become fertile adult mice. This is also true of chimeras composed of animal or vegetal pole cells derived through normal cleavage to the 8-cell stage. We discuss that although polarity of the postimplantation embryo can be traced back to the 8-cell stage and in turn to the organisation of the egg, it is not absolutely fixed by this time

The basal position of nuclei is one pre-requisite for asymmetric cell divisions in the early mouse embryo

The early mouse embryo undertakes two types of cell division: symmetric that gives rise to the trophectoderm and then placenta or asymmetric that gives rise to inner cells that generate the embryo proper. Although cell division orientation is important, the mechanism regulating it has remained unclear. Here, we identify the relationship between the plane of cell division and the position of the nucleus and go towards identifying the mechanism behind it. We first find that as the 8-cell embryo progresses through the cell cycle, the nuclei of most – but not all – cells move from apical to more basal positions, in a microtubule- and kinesin-dependent manner. We then find that all asymmetric divisions happen when nuclei are located basally and, in contrast, all cells, in which nuclei remain apical, divide symmetrically. To understand the potential mechanism behind this, we determine the effects of modulating expression of Cdx2, a transcription factor key for trophectoderm formation and cell polarity. We find that increased expression of Cdx2 leads to an increase in a number of apical nuclei, whereas down-regulation of Cdx2 leads to more nuclei moving basally, which explains a previously identified relationship between Cdx2 and cell division orientation. Finally, we show that down-regulation of aPKC, involved in cell polarity, decreases the number of apical nuclei and doubles the number of asymmetric divisions. These results suggest a model in which the mutual interdependence of Cdx2 and cell polarity affects the cytoskeleton-dependent positioning of nuclei and, in consequence, the plane of cell division in the early mouse embryo

Perceptual narrowing in speech and face recognition : evidence for intra-individual cross-domain relations

During the first year of life, infants undergo perceptual narrowing in the domains of speech and face perception. This is typically characterized by improvements in infants' abilities in discriminating among stimuli of familiar types, such as native speech tones and same-race faces. Simultaneously, infants begin to decline in their ability to discriminate among stimuli of types with which they have little experience, such as non-native tones and other-race faces. The similarity in time-frames during which perceptual narrowing seems to occur in the domains of speech and face perception has led some researchers to hypothesize that the perceptual narrowing in these domains could be driven by shared domain-general processes. To explore this hypothesis, we tested 53 Caucasian 9-month-old infants from monolingual German households on their ability to discriminate among non-native Cantonese speech tones, as well among same-race German faces and other-race Chinese faces. We tested the infants using an infant-controlled habituation-dishabituation paradigm, with infants' preferences for looking at novel stimuli versus the habituated stimuli (dishabituation scores) acting as indicators of discrimination ability. As expected for their age, infants were able to discriminate between same-race faces, but not between other-race faces or non-native speech tones. Most interestingly, we found that infants' dishabituation scores for the non-native speech tones and other-race faces showed significant positive correlations, while the dishabituation scores for non-native speech tones and same-race faces did not. These results therefore support the hypothesis that shared domain-general mechanisms may drive perceptual narrowing in the domains of speech and face perception

Perceptual narrowing in speech and face recognition : evidence for intra-individual cross-domain relations

During the first year of life, infants undergo perceptual narrowing in the domains of speech and face perception. This is typically characterized by improvements in infants' abilities in discriminating among stimuli of familiar types, such as native speech tones and same-race faces. Simultaneously, infants begin to decline in their ability to discriminate among stimuli of types with which they have little experience, such as non-native tones and other-race faces. The similarity in time-frames during which perceptual narrowing seems to occur in the domains of speech and face perception has led some researchers to hypothesize that the perceptual narrowing in these domains could be driven by shared domain-general processes. To explore this hypothesis, we tested 53 Caucasian 9-month-old infants from monolingual German households on their ability to discriminate among non-native Cantonese speech tones, as well among same-race German faces and other-race Chinese faces. We tested the infants using an infant-controlled habituation-dishabituation paradigm, with infants' preferences for looking at novel stimuli versus the habituated stimuli (dishabituation scores) acting as indicators of discrimination ability. As expected for their age, infants were able to discriminate between same-race faces, but not between other-race faces or non-native speech tones. Most interestingly, we found that infants' dishabituation scores for the non-native speech tones and other-race faces showed significant positive correlations, while the dishabituation scores for non-native speech tones and same-race faces did not. These results therefore support the hypothesis that shared domain-general mechanisms may drive perceptual narrowing in the domains of speech and face perception

Perceptual reorganization of lexical tones : effects of age and experimental procedure

Findings on the perceptual reorganization of lexical tones are mixed. Some studies report good tone discrimination abilities for all tested age groups, others report decreased or enhanced discrimination with increasing age, and still others report U-shaped developmental curves. Since prior studies have used a wide range of contrasts and experimental procedures, it is unclear how specific task requirements interact with discrimination abilities at different ages. In the present work, we tested German and Cantonese adults on their discrimination of Cantonese lexical tones, as well as German-learning infants between 6 and 18 months of age on their discrimination of two specific Cantonese tones using two different types of experimental procedures. The adult experiment showed that German native speakers can discriminate between lexical tones, but native Cantonese speakers show significantly better performance. The results from German-learning infants suggest that 6-and 18-month-olds discriminate tones, while 9-month-olds do not, supporting a U-shaped developmental curve. Furthermore, our results revealed an effect of methodology, with good discrimination performance at 6 months after habituation but not after familiarization. These results support three main conclusions. First, habituation can be a more sensitive procedure for measuring infants' discrimination than familiarization. Second, the previous finding of a U-shaped curve in the discrimination of lexical tones is further supported. Third, discrimination abilities at 18 months appear to reflect mature perceptual sensitivity to lexical tones, since German adults also discriminated the lexical tones with high accuracy

Polarity and cell division orientation in the cleavage embryo: from worm to human

Cleavage is a period after fertilization, when a 1-cell embryo starts developing into a multicellular organism. Due to a series of mitotic divisions, the large volume of a fertilized egg is divided into numerous smaller, nucleated cells—blastomeres. Embryos of different phyla divide according to different patterns, but molecular mechanism of these early divisions remains surprisingly conserved. In the present paper, we describe how polarity cues, cytoskeleton and cell-to-cell communication interact with each other to regulate orientation of the early embryonic division planes in model animals such as Caenorhabditis elegans, Drosophila and mouse. We focus particularly on the Par pathway and the actin-driven cytoplasmic flows that accompany it. We also describe a unique interplay between Par proteins and the Hippo pathway in cleavage mammalian embryos. Moreover, we discuss the potential meaning of polarity, cytoplasmic dynamics and cell-to-cell communication as quality biomarkers of human embryos