Control of Embryonic Cleavage Pattern

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.