Keratins are asymmetrically inherited fate determinants in the mammalian embryo

Lim, Hui Yi Grace; Álvarez, Yanina; Gasnier, Maxime; Wang, Yiming; Tetlak, Piotr; Bissière, Stéphanie; Wang, Hongmei; Biro, Maté; Plachta, Nicolas

doi:10.1038/s41586-020-2647-4

Cited by 87 publications

(77 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In epithelial tissues, desmosome-anchored KF form a mechanically resilient transcellular network that is modulated by and protects against physical stress 15 . In the mouse embryo, K8 and 18 are already detected in a subset of cells at the eight-cell stage 16 , and it was suggested that they function as asymmetrically inherited factors that specify the first trophectoderm cells 17 . Establishment of a knock-in K8-eYFP fusion mouse line allowed tracking KF network formation and dynamics in live embryos without functional alteration 18 .…”

Section: Introductionmentioning

confidence: 99%

Keratin dynamics govern the establishment of the maternal-fetal interface

Nahaboo

Eski²,

Vermeersch³

et al. 2021

Preprint

View full text Add to dashboard Cite

After implantation, the mouse embryo undergoes gastrulation and forms mesoderm and endoderm. Mesoderm participates in embryonic and extra-embryonic tissues including the amnion, yolk sac, chorion and allantois, the umbilical cord precursor. Extra-embryonic mesoderm is rich in intermediate filaments. Two-photon live imaging of keratin 8-eYFP knock-in embryos allowed recording nucleation and elongation of keratin filaments, which formed apical cables coordinated across multiple cells in amnion, allantois, and blood islands. Embryos lacking all keratins displayed a deflated exocoelomic cavity, a narrow thick amnion, and a short allantois, indicating a hitherto unknown role for keratin filaments in post-implantation extra-embryonic membranes morphogenesis. Single-cell RNA sequencing of mesoderm cells, microdissected amnion, chorion, and allantois provided an interactive atlas of transcriptomes with germ layer and regional information. Keratin 8high mesenchymal cells in contact with the exocoelom shared a cytoskeleton and adhesion expression profile that might explain the adaptation of extra-embryonic structures to the increasing mechanical pressure.

show abstract

Section: Introductionmentioning

confidence: 99%

Keratin dynamics govern the establishment of the maternal-fetal interface

Nahaboo

Eski²,

Vermeersch³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Vice versa, PARD6B depletion impaired keratin polarization at the apical site and instead promoted the symmetrical inheritance of keratins. This indicates that the apical localization of keratins and classical polarity proteins creates a polymer-based polarity memory as an early event during lineage specification (Lim et al, 2020). Interestingly, also alterations in embryo size by means of blastocoel volume oscillations and concomitant changes in trophectoderm cortical tension contribute to asymmetric fate determination in mouse blastocysts (Chan et al, 2019).…”

Section: Coupling Of Polarity Cytoskeleton and Tension Anisotropy During Early Lineage Commitment In Mammalian Embryosmentioning

confidence: 99%

“…Indeed, for example in the early mouse blastocyst, the inner cell mass (ICM) is established by translocation of nonpolarized cells to the centre of the embryo, clearly separating from the trophectoderm, which is composed of polarized cells. Several polarity proteins are apically enriched in trophectoderm cells, and loss-of-function experiments suggested a role for Par3 (Plusa et al, 2005), Par6B (Alarcon, 2010;Hirate et al, 2013;Lim et al, 2020) and aPKC (Plusa et al, 2005;Hirate et al, 2013;Maître et al, 2016) isoforms in lineage allocation. For long, spindle orientation was considered the major mechanism of asymmetric cell division during ICM allocation.…”

Section: Coupling Of Polarity Cytoskeleton and Tension Anisotropy During Early Lineage Commitment In Mammalian Embryosmentioning

confidence: 99%

Orchestration of tissue‐scale mechanics and fate decisions by polarity signalling

Gomes

Iden

2021

The EMBO Journal

View full text Add to dashboard Cite

Eukaryotic development relies on dynamic cell shape changes and segregation of fate determinants to achieve coordinated compartmentalization at larger scale. Studies in invertebrates have identified polarity programmes essential for morphogenesis; however, less is known about their contribution to adult tissue maintenance. While polarity-dependent fate decisions in mammals utilize molecular machineries similar to invertebrates, the hierarchies and effectors can differ widely. Recent studies in epithelial systems disclosed an intriguing interplay of polarity proteins, adhesion molecules and mechanochemical pathways in tissue organization. Based on major advances in biophysics, genome editing, highresolution imaging and mathematical modelling, the cell polarity field has evolved to a remarkably multidisciplinary ground. Here, we review emerging concepts how polarity and cell fate are coupled, with emphasis on tissue-scale mechanisms, mechanobiology and mammalian models. Recent findings on the role of polarity signalling for tissue mechanics, micro-environmental functions and fate choices in health and disease will be summarized.

show abstract

“…Recently it has been found that conserved mechanisms specify the TE in mouse and human. [21,141,142] From the 8-cell stage, the outer cells via the asymmetrical inheritance of keratin filaments [143,144] acquire an apical-basal cell polarity with atypical protein kinase C expression at the peripheral cell membrane, nuclear Yap1, and restricted expression of TE factors. [21] However, in contrast to mouse, it takes in human until the blastocyst stage to restrict plasticity in TE cells, due to retention of pluripotency genes such as Oct4 and Sox2.…”

Section: Drawing Parallels Between Mouse and Human Pre-implantation Dmentioning

confidence: 99%

From Snapshots to Development: Identifying the Gaps in the Development of Stem Cell‐based Embryo Models along the Embryonic Timeline

et al. 2021

View full text Add to dashboard Cite

In recent years, stem cell-based models that reconstruct mouse and human embryogenesis have gained significant traction due to their near-physiological similarity to natural embryos. Embryo models can be generated in large numbers, provide accessibility to a variety of experimental tools such as genetic and chemical manipulation, and confer compatibility with automated readouts, which permits exciting experimental avenues for exploring the genetic and molecular principles of self-organization, development, and disease. However, the current embryo models recapitulate only snapshots within the continuum of embryonic development, allowing the progression of the embryonic tissues along a specific direction. Hence, to fully exploit the potential of stem cell-based embryo models, multiple important gaps in the developmental landscape need to be covered. These include recapitulating the lesser-explored interactions between embryonic and extraembryonic tissues such as the yolk sac, placenta, and the umbilical cord; spatial and temporal organization of tissues; and the anterior patterning of embryonic development. Here, it is detailed how combinations of stem cells and versatile bioengineering technologies can help in addressing these gaps and thereby extend the implications of embryo models in the fields of cell biology, development, and regenerative medicine.

show abstract

Keratins are asymmetrically inherited fate determinants in the mammalian embryo

Cited by 87 publications

References 50 publications

Keratin dynamics govern the establishment of the maternal-fetal interface

Keratin dynamics govern the establishment of the maternal-fetal interface

Orchestration of tissue‐scale mechanics and fate decisions by polarity signalling

From Snapshots to Development: Identifying the Gaps in the Development of Stem Cell‐based Embryo Models along the Embryonic Timeline

Contact Info

Product

Resources

About