Whole population cell analysis of a landmark-rich mammalian epithelium reveals multiple elongation mechanisms

Citations Over TimeTop 12% of 2013 papers

Abstract

Tissue elongation is a fundamental component of developing and regenerating systems. Although localised proliferation is an important mechanism for tissue elongation, potentially important contributions of other elongation mechanisms, specifically cell shape change, orientated cell division and cell rearrangement, are rarely considered or quantified, particularly in mammalian systems. Their quantification, together with proliferation, provides a rigorous framework for the analysis of elongation. The mammalian palatal epithelium is a landmark-rich tissue, marked by regularly spaced ridges (rugae), making it an excellent model in which to analyse the contributions of cellular processes to directional tissue growth. We captured confocal stacks of entire fixed mouse palate epithelia throughout the mid-gestation growth period, labelled with membrane, nuclear and cell proliferation markers and segmented all cells (up to ∼20,000 per palate), allowing the quantification of cell shape and proliferation. Using the rugae as landmarks, these measures revealed that the so-called growth zone is a region of proliferation that is intermittently elevated at ruga initiation. The distribution of oriented cell division suggests that it is not a driver of tissue elongation, whereas cell shape analysis revealed that both elongation of cells leaving the growth zone and apico-basal cell rearrangements do contribute significantly to directional growth. Quantitative comparison of elongation processes indicated that proliferation contributes most to elongation at the growth zone, but cell shape change and rearrangement contribute as much as 40% of total elongation. We have demonstrated the utility of an approach to analysing the cellular mechanisms underlying tissue elongation in mammalian tissues. It should be broadly applied to higher-resolution analysis of links between genotypes and malformation phenotypes.

Related Papers

• → Cell‐cell signaling by direct contact increases cell proliferation via a PI3K‐dependent signal(2002)264 cited
• → The role of cell‐cell contact in “contact” inhibition of cell division: A review and new evidence(1972)153 cited
• → Cell division and cell allocation in early mouse development(1978)156 cited
• → Origin of Individuality of Two Daughter Cells during the Division Process Examined by the Simultaneous Measurement of Growth and Swimming Property Using an On-Chip Single-Cell Cultivation System(2007)28 cited
• → The mode of action of 2,4-D in counter-acting the elongation of carrot cells grown in culture(1980)36 cited