The membrane that surrounds the embryo in the earliest stage of development
Study provides previously hidden insights into the origin of human life
A MedUni Vienna study team led by geneticist Markus Hengstschläger has used a stem cell model to model the earliest stages of embryonic development and to characterize the membrane that surrounds the embryo, conferring shape and stability. This membrane is responsible for the specification and organization of the embryo's cells and allows it to grow in a controlled manner. The findings form the basis for further research with the aim to better understand the causes of abnormal embryonic development. The results were recently published in the top journal Developmental Cell.
Approximately every second human embryo is affected by an abnormal development which, for example, causes the embryo not being able to implant into the uterus or results in a miscarriage. In addition to maternal factors or genetic abnormalities of the embryo (the latter can be investigated using pre-implantation genetic diagnosis in the course of in-vitro-fertilization (IVF)), it can also be assumed that aberrations of the cellular order and morphology of the embryo could play a role. The causes of such aberrations have not yet been clarified, particularly because research on human embryos is prohibited by law in many countries around the world, including Austria, for ethical reasons.
Markus Hengstschläger, Head of the Institute of Medical Genetics at MedUni Vienna, leads one of a few laboratories worldwide that are capable of generating models of the human embryo from pluripotent stem cells in a Petri dish, so-called embryoids. Using such embryoids, which have only recently become available and cannot develop into a human being, the researchers are now able to model and to explore the earliest developmental phases of human life.
In a study published in Developmental Cell, the world’s leading journal for developmental biology, the two authors Margit Rosner and Markus Hengstschläger have now succeeded in showing for the first time that the modelled human embryo itself produces a membrane (basement membrane) that surrounds the developing embryo, without which it cannot survive and which is responsible for the way it looks. This membrane gives the embryo shape and stability, is responsible for the specification and organization of the embryo's cells and allows it to grow in a controlled manner.
Gene responsible for the development of the basement membrane identified
In addition, the authors have identified Oct4 from thousands of human genes as one gene that is significantly involved in the formation and development of this basement membrane. With this, they have thus been able to assign a previously undescribed function to this transcription factor.
"This study sheds light on molecular mechanisms that are of great importance for the development of human life and forms the basis for further research with the aim to better understand the causes of those aberrations that cause the human embryo not being able to initiate a pregnancy or lead to a miscarriage," explains Markus Hengstschläger, "in addition, many human diseases have their origin in early embryonic development. However, we still know very little about this relation because until now early human development has been completely inaccessible to research."
Publication: Developmental Cell
Oct4 controls basement membrane development during human embryogenesis;
Rosner M., Hengstschläger M. (2024).
DOI: https://doi.org/10.1016/j.devcel.2024.03.007
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