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Feb 17, 2025
From 11:30 AM to 12:30 PM

Location 110, avenue des Pins ouestMontréal, H2W 1R7
ContactAngela Durant, Student records management technician
IRCM Early-Career Scientist Seminar

Ashley Libby

Ashley Libby

CRISPy Chickens - Genetically coordinated cell fate transitions in neural tube development

Ashley Libby, PhD
Postdoctoral Fellow

The Francis Crick Institute 
London, United Kingdom

This conference is hosted by François Robert, PhD. This conference is part of the the IRCM Early-Career Scientist Seminar Series (ECS3), a groundbreaking initiative whose mission is to showcase early career scientists. This is a great opportunity to discover the exciting projects of these researchers in training in front of a multidisciplinary audience.


About this conference
Development relies on the coordinated differentiation of stem cells in dynamically changing environments. An excellent example is vertebrate neural tube formation. Here, stem cells transition through a dynamic signalling landscape to form neural tissue where the detailed gene regulatory mechanisms remain ill-defined. To address this, we developed and performed a multiplexed in vivo single-cell perturbation screen in chick embryos of genes that change in their expression with acquisition of the neural tube lineage. This revealed a role for the gene MLLT3, a component of the super elongation complex, in specification of neural identity. Perturbation of MLLT3 resulted in knockout cells adopting a lateral plate mesoderm fate over that of the neural tube causing kinked spines. We discovered that MLLT3 depletion caused misregulation of genes involved in Wnt and Retinoic Acid (RA) signalling, key regulatory pathways of neural fate. We then compared the effect of MLLT3 loss to the forced expression of mutant RARa, either lacking the MLLT3 binding domain or consisting of only the MLLT3 binding region. In all cases, neural tube progenitors were depleted, resulting in smaller neural tubes. However, only MLLT3 loss caused disruption of the stem cell compartment, indicating a dual role of stem cell maintenance coupled with RA driven neural fate acquisition. Together this data demonstrates a system appropriate for performing in vivo CRISPR screens in chick embryos and identifies a previous unanticipated role for MLLT3. More broadly, it highlights a mechanistic gene regulatory strategy of lineage emergence in a dynamic signalling landscape.

About Ashley Libby
Dr. Ashley Libby completed her PhD in Developmental and Stem Cell Biology at the University of California, San Francisco, working under the mentorship of Drs. Bruce Conklin and Todd McDevitt. Her doctoral research focused on gastrulation patterning using induced pluripotent stem cell models, developing CRISPR-based assays, machine learning classifiers, and 3D organoid systems to study self-directed multicellular organization and morphogenesis. Currently, Dr. Libby is a postdoctoral researcher in the Briscoe Lab at the Francis Crick Institute. She investigates the genetic mechanisms underlying tissue production and stem cell fate determination during neural tube development.

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