University of Cambridge > Talks.cam > Morphogenesis Seminar Series > CRISPy Chickens-screening fate transitions from caudal epiblast to neural tube-Ashley Libby; Coupling mitochondrial energy metabolism to branching morphogenesis in the developing avian lung-Bezia Lemma.

CRISPy Chickens-screening fate transitions from caudal epiblast to neural tube-Ashley Libby; Coupling mitochondrial energy metabolism to branching morphogenesis in the developing avian lung-Bezia Lemma.

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  • UserAshley Libby, Briscoe lab,The Francis Crick Institute; and Bezia Lemma, Nelson lab, Princeton University
  • ClockMonday 26 February 2024, 14:30-15:30
  • HouseOnline.

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Title: CRIS Py Chickens-screening fate transitions from caudal epiblast to neural tube-Ashley Libby

Abstract:

A remarkable aspect of embryonic development is the coordinated emergence of multiple cell populations in dynamically changing tissues. For example, neural tube development requires a flat structure of epiblast cells to generate a final closed neural tube structure, that has genetically stratified progenitor domains. This involves the physical folding and elongation of the tissue, which positions cells within varying gradients of high Wnt/FGF in epiblast to high retinoic acid in the closed neural tube. At the same time, within this rapidly changing environment, transcription factor regulation defines end populations in a robustly programmed pattern. However, despite an overall morphogenic understanding of this process, the molecular mechanisms that specify and coordinate progenitor transitions between the epiblast and neural tube remain ill-defined.

I will talk about how my research investigates both changes in tissue architecture and cell fate decisions by pairing single-cell imaging and genetic screen techniques. I will show multi-photon images and videos of chick embryos to highlight how cells move as the neural tube is closing, focusing on a gradient of decreasing lateral cell movement as cells progress from the epiblast to neural tube. In complement, I will also talk about the design of a small in vivo pooled CRISPR screen in chick embryos, to examine how intrinsically changing a cell’s receptiveness to morphogenic signalling affects later acquired fates. Here, I will talk about how we found epigenetic/transcriptional regulators that facilitate the rapid interpretation/response to the changes in FGF and retinoic acid to genetically guide rapid fate specification.

Overall, this work highlights several strategies, physical and epigenetic, by which the embryo coordinates cell fate in a dynamic signalling environment to form robust patterning and thus functional tissues.

Title: Coupling mitochondrial energy metabolism to branching morphogenesis in the developing avian lung-Bezia Lemma

Abstract: Energy metabolism at a molecular scale is required to fuel cellular activity that gives rise to tissue morphogenesis. However it is unclear whether energy metabolism is patterned during organogenesis in a way that influences or aligns with gene expression and mechanical forces. We have measured the spatial patterns of mitochondrial membrane density, membrane potential, and ATP concentration in the embryonic chicken lung. At this stage of development, the chicken lung is comprised of tubes of simple columnar epithelium surrounded by a loose mesenchyme. To generate the first several branches off the dorsal surface of the primary bronchus, subsets of epithelial cells undergo actomyosin-driven apical constriction. The first three of these branching events are highly stereotyped in time and location; we therefore focused on this geometrically ideal system to study how energy metabolism relates to changes in tissue morphology. Our results reveal heightened mitochondrial energy metabolism specifically in epithelial areas of initiating branches. Additionally, we measured oxygen consumption rates to set physical bounds on the levels of total mitochondrial respiration. These findings establish a connection between the patterning of energy metabolism and the morphogenesis of multicellular tissues. This work is funded in part by an NIH Director’s Pioneer Award (HD111539) and the NSF PRFB Grant No. (2305831)

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This talk is part of the Morphogenesis Seminar Series series.

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