University of Cambridge > Talks.cam > Morphogenesis Seminar Series > Jamie: "A biomechanical switch regulates the transition towards homeostasis in oesophageal epithelium" Ben: "Integrating pattern formation and cell movements in our understanding of morphogenesis"

Jamie: "A biomechanical switch regulates the transition towards homeostasis in oesophageal epithelium" Ben: "Integrating pattern formation and cell movements in our understanding of morphogenesis"

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  • UserBen Steventon, Jamie McGinn
  • ClockMonday 08 November 2021, 14:30-15:30
  • HouseOnline.

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Jamie McGinn Mounting evidence suggests that epithelial stem cells are more dynamic than originally thought. Stem cell behaviour is not a discrete state as it can be re-gained by differentiating cells as a result of tissue challenges such as injury and tumorigenesis. This plasticity may explain why, despite decades of intensive research in epithelial stem cell biology, the field still debates about the identity of the cell populations contributing to the homeostasis and repair of squamous tissues. In order to fully unveil the rules governing epithelial cell behaviour, it is critical to understand the dynamic nature of epithelial cells by exploring their response to situations away from homeostasis. In this study we investigate the cell fate transitions taking place in the mouse squamous oesophageal epithelium from birth until the onset of adult homeostasis, as a physiological model of rapid but restricted tissue growth. Observations throughout post-natal development show that oesophageal expansion after birth occurs in a biphasic pattern, with a fast initial growth that slows down before reaching adult tissue size. This turning point is characterized by a range of changes in the expression of key developmental factors, defining the transition of cell fate identity in the basal progenitor cell compartment. The establishment of homeostatic oesophageal features coincide with significant changes in tissue architecture, including tissue strain and decreased cell density. Remarkably, tissue stretching experiments reveal that the mechanical changes experienced by the developing oesophageal epithelium after birth are critical for shifting the rapid growing tissue into a homeostatic mode.

Ben Steventon As cells proceed through development, information contained in the genome is expressed in a context-dependent manner. This must be regulated precisely in both space and time to generate patterns of gene expression that set-up the spatial coordinates of tissue and organ primordia that build the embryo. Our current understanding of pattern formation relies on the concept of positional information, the idea that cells receive instructive signals that impart a spatial coordinate system to generate pattern. While this model works very well in static cell populations with minimal cell rearrangement, it becomes challenging when considering dynamic morphogenetic processes such as gastrulation. Furthermore, pattern formation in gastrulation is highly flexible to alterations in the size, scale and spatial rearrangement of cells in both experimental and evolutionary situations. Our work seeks to provide illustrations of two concepts that will help resolve these long-standing problems of pattern regulation, evolvability and self-organisation. Firstly, downward causation emphasises the role that multi-tissue interactions play in relaying information from changes at the organ and organism level to the regulation of gene regulatory networks (GRNs) at the cell level. Secondly, pattern emergence considers how extracellular signals act to control the dynamics of autonomous GRN activity, rather than as instructive signals to direct cell fate transitions. In this sense, we propose that pattern formation should not be seen as a downstream output of organisers and their responding tissues, but rather as an emergent property of their dynamic interaction.

This talk is part of the Morphogenesis Seminar Series series.

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