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Control of Embryonic Cleavage Pattern

Control of Embryonic Cleavage Pattern

Carl-Philipp Heisenberg (ORCID: 0000-0002-0912-4566)
  • Grant DOI 10.55776/I3601
  • Funding program Principal Investigator Projects International
  • Status ended
  • Start May 1, 2018
  • End April 30, 2022
  • Funding amount € 228,910
  • Project website
  • E-mail

Bilaterale Ausschreibung: Frankreich

Disciplines

Biology (100%)

Keywords

    Morphogenesis, Ascidian, Cell Mechanics, Cell Division

Abstract Final report

To obtain insight into how mechanical and biomolecular mechanisms lead to the emergence of organismal shape we propose examining an organism with a small number of cells and where the axis of every cell division is fixed and thus predictable. The European ascidian Phallusia mammillata has transparent embryos, develops with a small cell number (64-cell blastula), and displays an invariant cleavage pattern making it ideal to study the role of cell division in organismal morphogenesis. Previous studies have suggested that all division axes during early stages of Phallusia development are determined by a combination of cell shape and apicobasal cell polarization. Yet, how cell polarization and shape function together to determine spindle positioning and thus cell division orientation remains unclear. Here we propose elucidating the interaction and feedback between the molecular, cellular and physical mechanisms determining cell shape and polarity, and how those mechanisms control cell division orientation during the emergence of organismal shape.

Cell division is a fundamental process in the development of all multicellular organisms. It determines the shape and size of the developing organism, and influences how cells differentiate into different cell types. Defects in cell division not only lead to abnormal development, but also represent the basis for the formation of tumours and metastases, a hallmark of cancer. In our study, we have investigated the molecular, cellular and biophysical mechanisms that determine the orientation of the first cell cleavages in the development of chordates. To this end, we have used ascidian embryos (Phallusia mammillata), a popular model organism in developmental biology, for studying this process. We were able to show that two key factors determine how cells in the early ascidian embryo divide and thus the early embryo develops: (1) the shape of the dividing cell, which again determines the position of the mitotic spindle and thus cell division orientation; (2) die polarised subcellular localisation of molecular cues in the dividing cell, which directly couple the mitotic spindle to the cell cortex and thus determine cell division orientation. Interestingly, we found that these two key factors display a common, rather than antagonistic effect on cell division orientation. This is an unexpected finding, given that previous studies had suggested that only one of these two factors, but not both of them together, decisively influence cell division orientation. The result of our present study provide insight into the mechanistic basis of embryonic development. Even more generally, they advance our understanding of the regulation of cell division, defects of which play a decisive role in the formation of tumours and metastases in cancer. In future studies, one should investigate how cell shape and the polarised distribution of molecular cues within the dividing cell influence each other: does cell shape directly influence where within the dividing cell moleculr cues importaznt for cell division orientation localize? Does the molecular polarisation of cells influence cell shape by e.g. determining the deformability of cells? The present study has laid the basis for answering these questions.

Research institution(s)
  • Institute of Science and Technology Austria - ISTA - 100%
International project participants
  • Alexander Mcdougall, Universite Pierre et Marie Curie - France

Research Output

  • 83 Citations
  • 5 Publications
  • 1 Scientific Awards
  • 1 Fundings
Publications
  • 2024
    Title Friction forces determine cytoplasmic reorganization and shape changes of ascidian oocytes upon fertilization
    DOI 10.1038/s41567-023-02302-1
    Type Journal Article
    Author Caballero-Mancebo S
    Journal Nature Physics
    Pages 310-321
    Link Publication
  • 2021
    Title Combined effect of cell geometry and polarity domains determines the orientation of unequal division
    DOI 10.7554/elife.75639
    Type Journal Article
    Author Godard B
    Journal eLife
    Link Publication
  • 2020
    Title Apical Relaxation during Mitotic Rounding Promotes Tension-Oriented Cell Division
    DOI 10.1016/j.devcel.2020.10.016
    Type Journal Article
    Author Godard B
    Journal Developmental Cell
    Link Publication
  • 2021
    Title Combined effect of cell geometry and polarity domains determines the orientation of unequal division
    DOI 10.1101/2021.05.04.442692
    Type Preprint
    Author Godard B
    Pages 2021.05.04.442692
    Link Publication
  • 2019
    Title Zebrafish gastrulation: Putting fate in motion
    DOI 10.1016/bs.ctdb.2019.10.009
    Type Book Chapter
    Author Pinheiro D
    Publisher Elsevier
    Pages 343-375
Scientific Awards
  • 2019
    Title Carus Medal
    Type Medal
    Level of Recognition National (any country)
Fundings
  • 2018
    Title Control of Embryonic Cleavage Pattern
    Type Other
    Start of Funding 2018
    Funder Austrian Science Fund (FWF)

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