Downregulation of Extraembryonic Tension Controls Body Axis Formation in Avian Embryos

Embryonic tissues undergoing shape change draw mechanical input from extraembryonic substrates. In avian eggs, the early blastoderm disk is under the tension of the vitelline membrane (VM). Here we report that chicken VM characteristically downregulates tension and stiffness to facilitate stage-specific embryo morphogenesis. While early relaxation of the VM impairs blastoderm expansion, maintaining VM tension in later stages resists the convergence of the posterior body causing stalled elongation, open neural tube, and axis rupture. Biochemical and structural analysis shows that VM weakening follows the reduction of its outer-layer glycoprotein fibers, which is caused by an increasing albumen pH due to CO2 release from the egg. Our results identify a previously unrecognized mechanism of body axis defects through mis-regulation of extraembryonic tissue tension.

A sexual dimorphic role of the miR-465 cluster in placental development

A sexually dimorphic role of miRNAs in placental development has never been reported. Here, we show that ablation of the miR-465 cluster caused selective degeneration of female conceptuses as early as embryonic day (E)8.5, leading to a male-biased sex ratio (60% males) among miR-465 KO mice. Given that the miR-465 cluster miRNAs were predominantly expressed in the extraembryonic tissue and ablation of these miRNAs led to dysregulation of numerous critical placental genes, our data strongly suggest the miR-465 cluster is required for full developmental potential of the female, but not the male, extraembryonic tissue/placenta.

Regionalized tissue fluidization is required for epithelial gap closure during insect gastrulation

Many animal embryos pull and close an epithelial sheet around the ellipsoidal egg surface during a gastrulation process known as epiboly. The ovoidal geometry dictates that the epithelial sheet first expands and subsequently compacts. Moreover, the spreading epithelium is mechanically stressed and this stress needs to be released. Here we show that during extraembryonic tissue (serosa) epiboly in the insect Tribolium castaneum, the non-proliferative serosa becomes regionalized into a solid-like dorsal region with larger non-rearranging cells, and a more fluid-like ventral region surrounding the leading edge with smaller cells undergoing intercalations. Our results suggest that a heterogeneous actomyosin cable contributes to the fluidization of the leading edge by driving sequential eviction and intercalation of individual cells away from the serosa margin. Since this developmental solution utilized during epiboly resembles the mechanism of wound healing, we propose actomyosin cable-driven local tissue fluidization as a conserved morphogenetic module for closure of epithelial gaps.

Developmentally Delayed Epigenetic Reprogramming Underlying the Pathogenesis of Preeclampsia

SummaryPreeclampsia, a life-threatening pregnancy complication characterized by hypertension and multiorgan damage, affects 2-5% of pregnancies and causes 76,000 deaths per year. Most preeclampsia associated syndromes immediately dispel after removal of placenta, indicating a casual role of placenta in the pathogenesis. Failed transformation of spiral artery due to insufficient invasion and excessive apoptosis of trophoblast suggested developmental defects in preeclampsia placenta. However, the underlying molecular mechanisms that affected placenta development in preeclampsia remained elusive. Here we show that, in preeclampsia placenta, the epigenetic landscape formed during extraembryonic tissue differentiation was disrupted: dramatic chromatin accessibility shift affected known and novel genes implicated in preeclampsia. DNA methylation defects in preeclampsia affected lineage-defining PcG-controlled loci in trophectoderm. LTR12 retrotransposons associated with VCT/SCT-specific genes were hypermethylated. Meanwhile, hundreds of PcG-regulated EVT-specific gene promoters, which otherwise undergone post-ZGA extraembryonic-tissue-specific de novo methylation, were hypomethylated and hyper-activated. Together, these epigenetic defects resulted in placenta developmental delay in preeclampsia. The defective methylation pattern could be detected in serum cfDNA, and could be used to accurately predict preeclampsia at early pregnancy weeks in independent validation cohorts. Our data suggests that the preeclampsia placenta represents a stalled state of epigenetic reprogramming en route of development from trophectoderm to normal placenta.

Regionalized tissue fluidization by an actomyosin cable is required for epithelial gap closure during insect gastrulation

ABSTRACTMany animal embryos pull and close an epithelial sheet around the spherical or ellipsoidal egg surface during a gastrulation process known as epiboly. The ovoidal geometry dictates that the epithelial sheet first expands and subsequently compacts. Moreover, the epithelial sheet spreading over the sphere is mechanically stressed and this stress needs to be released. Here we show that during extraembryonic tissue (serosa) epiboly in the red flour beetle Tribolium castaneum, the non-proliferative serosa becomes regionalized into two distinct territories: a dorsal region under higher tension away from the leading edge with larger non-rearranging cells, and a more fluid ventral region under lower tension surrounding the leading edge with smaller cells undergoing cell intercalation. Our results suggest that fluidization of the leading edge is caused by a heterogeneous actomyosin cable that drives sequential eviction and intercalation of individual cells away from the serosa margin. Since this developmental solution utilized during epiboly resembles the mechanism of wound healing in other systems, we propose actomyosin cable-driven local tissue fluidization as a conserved morphogenetic module for closure of epithelial gaps.

Decoupling from yolk sac is required for extraembryonic tissue spreading in the scuttle fly Megaselia abdita

ABSTRACTExtraembryonic tissues contribute to animal development, which often entails spreading over embryo or yolk. Apart from changes in cell shape, the requirements for this tissue spreading are not well understood. Here we analyze spreading of the extraembryonic serosa in the scuttle fly Megaselia abdita. The serosa forms from a columnar blastoderm anlage, becomes a squamous epithelium, and eventually spreads over the embryo proper. We describe the dynamics of this process in long-term, whole-embryo time-lapse recordings, demonstrating that free serosa spreading is preceded by a prolonged pause in tissue expansion. Closer examination of this pause reveals mechanical coupling to the underlying yolk sac, which is later released. We find mechanical coupling prolonged and serosa spreading impaired after knockdown of M. abdita Matrix metalloprotease 1. We conclude that tissue-tissue interactions provide a critical functional element to constrain spreading epithelia.Impact StatementExtraembryonic tissue spreading in the scuttle fly Megaselia abdita requires mechanical decoupling from the underlying yolk sac.

Zebrafish yolk syncytial nuclei migrate along a dynamic microtubule network

In teleosts, the yolk syncytial layer is a multinucleate syncytium that functions as an extraembryonic signaling center to pattern the mesendoderm, coordinate morphogenesis and supply nutrients to the embryo. The zebrafish is an excellent system for studying this morphogenetically active tissue. The external yolk syncytial nuclei (e-YSN) undergo microtubule dependent epiboly movements that distribute the nuclei over the yolk. How e-YSN epiboly proceeds, and what role the yolk microtubule network plays is not understood but currently it is proposed that e-YSN are pulled vegetally as the microtubule network shortens from the vegetal pole. Data from our live imaging studies suggest that the yolk microtubule network is dismantled from the animal and vegetal regions and show that a region of stabilized microtubules forms before nuclear migration begins. e-YSN do not appear to be pulled vegetally but rather move along a dynamic microtubule network. We also show that overexpression of the KASH domain of Syne2a impairs e-YSN movement, implicating the LINC complex in e-YSN migration. This work provides new insights into the role of microtubules in morphogenesis of an extraembryonic tissue.Summary StatementAnalysis of yolk syncytial nuclear migration during zebrafish epiboly reveals that nuclei migrate along and largely beneath a dynamically yolk microtubule network.

Cell–cell and cell–extracellular matrix adhesions cooperate to organize actomyosin networks and maintain force transmission during dorsal closure

Tissue morphogenesis relies on the coordinated action of actin networks, cell–cell adhesions, and cell–extracellular matrix (ECM) adhesions. Such coordination can be achieved through cross-talk between cell–cell and cell–ECM adhesions. Drosophila dorsal closure (DC), a morphogenetic process in which an extraembryonic tissue called the amnioserosa contracts and ingresses to close a discontinuity in the dorsal epidermis of the embryo, requires both cell–cell and cell–ECM adhesions. However, whether the functions of these two types of adhesions are coordinated during DC is not known. Here we analyzed possible interdependence between cell–cell and cell–ECM adhesions during DC and its effect on the actomyosin network. We find that loss of cell–ECM adhesion results in aberrant distributions of cadherin-mediated adhesions and actin networks in the amnioserosa and subsequent disruption of myosin recruitment and dynamics. Moreover, loss of cell–cell adhesion caused up-regulation of cell–ECM adhesion, leading to reduced cell deformation and force transmission across amnioserosa cells. Our results show how interdependence between cell–cell and cell–ECM adhesions is important in regulating cell behaviors, force generation, and force transmission critical for tissue morphogenesis.