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SUMMARY:Jamie: &quot\;A biomechanical switch regulates the transition towa
 rds homeostasis in oesophageal epithelium&quot\;     Ben: &quot\;Integrati
 ng pattern formation and cell movements in our understanding of morphogene
 sis&quot\; - Ben Steventon\, Jamie McGinn
DTSTART:20211108T143000Z
DTEND:20211108T153000Z
UID:TALK162514@talks.cam.ac.uk
CONTACT:102601
DESCRIPTION:*Jamie McGinn*\nMounting evidence suggests that epithelial ste
 m cells are more dynamic than originally thought. Stem cell behaviour is n
 ot a discrete state as it can be re-gained by differentiating cells as a r
 esult of tissue challenges such as injury and tumorigenesis. This plastici
 ty may explain why\, despite decades of intensive research in epithelial s
 tem 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 ex
 ploring their response to situations away from homeostasis. In this study 
 we investigate the cell fate transitions taking place in the mouse squamou
 s oesophageal epithelium from birth until the onset of adult homeostasis\,
  as a physiological model of rapid but restricted tissue growth. Observati
 ons throughout post-natal development show that oesophageal expansion afte
 r birth occurs in a biphasic pattern\, with a fast initial growth that slo
 ws down before reaching adult tissue size. This turning point is character
 ized by a range of changes in the expression of key developmental factors\
 , defining the transition of cell fate identity in the basal progenitor ce
 ll compartment. The establishment of homeostatic oesophageal features coin
 cide with significant changes in tissue architecture\, including tissue st
 rain and decreased cell density. Remarkably\, tissue stretching experiment
 s reveal that the mechanical changes experienced by the developing oesopha
 geal epithelium after birth are critical for shifting the rapid growing ti
 ssue into a homeostatic mode. \n\n*Ben Steventon*\nAs cells proceed throug
 h development\, information contained in the genome is expressed in a cont
 ext-dependent manner. This must be regulated precisely in both space and t
 ime to generate patterns of gene expression that set-up the spatial coordi
 nates of tissue and organ primordia that build the embryo. Our current und
 erstanding of pattern formation relies on the concept of positional inform
 ation\, the idea that cells receive instructive signals that impart a spat
 ial coordinate system to generate pattern. While this model works very wel
 l in static cell populations with minimal cell rearrangement\, it becomes 
 challenging when considering dynamic morphogenetic processes such as gastr
 ulation. Furthermore\, pattern formation in gastrulation is highly flexibl
 e to alterations in the size\, scale and spatial rearrangement of cells in
  both experimental and evolutionary situations.  \nOur work seeks to provi
 de illustrations of two concepts that will help resolve these long-standin
 g problems of pattern regulation\, evolvability and self-organisation. Fir
 stly\, downward causation emphasises the role that multi-tissue interactio
 ns play in relaying information from changes at the organ and organism lev
 el to the regulation of gene regulatory networks (GRNs) at the cell level.
  Secondly\, pattern emergence considers how extracellular signals act to c
 ontrol the dynamics of autonomous GRN activity\, rather than as instructiv
 e 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 thei
 r dynamic interaction. 
LOCATION:Online
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