An in vivo CRISPR screen in chick embryos reveals a role for MLLT3 in specification of neural cells from the caudal epiblast.

Ashley R G Libby, Tiago Rito, Arthur Radley, James Briscoe

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Article in Development (Cambridge, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

4 authors.

Ashley R G LibbyThe Francis Crick Institute, Developmental Dynamics Group, 1 Midland Rd, London, NW1 1AT, UK.ORCID 0000-0002-8139-8844

Tiago RitoThe Francis Crick Institute, Developmental Dynamics Group, 1 Midland Rd, London, NW1 1AT, UK.

Arthur RadleyThe Francis Crick Institute, Developmental Dynamics Group, 1 Midland Rd, London, NW1 1AT, UK.

James BriscoeThe Francis Crick Institute, Developmental Dynamics Group, 1 Midland Rd, London, NW1 1AT, UK.ORCID 0000-0002-1020-5240

Funding

European Molecular Biology Organization ALTF 149-2020European Research CouncilFrancis Crick InstituteHorizon 2020 742138Wellcome 226633/Z/22/ZWellcome Trust

6 · The paper itself

Abstract

Tissue development relies on the coordinated differentiation of stem cells in dynamically changing environments. The formation of the vertebrate neural tube from stem cells in the caudal lateral epiblast is a well-characterized example. Despite an understanding of the signalling pathways involved, the gene regulatory mechanisms remain poorly defined. To address this, we developed a multiplexed in vivo CRISPR screening approach in chick embryos targeting genes expressed in the caudal epiblast and neural tube. This revealed a role for MLLT3, a component of the super elongation complex, in the specification of neural fate. Perturbation of MLLT3 disrupted neural tube morphology and reduced neural fate acquisition. Mutant forms of retinoic acid receptor A lacking the MLLT3 binding domain similarly reduced neural fate acquisition. Together, these findings validate an in vivo CRISPR screen strategy in chick embryos and identify a previously unreported role for MLLT3 in caudal neural tissue specification.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsGerm LayersNeural Stem CellsNeuronsAnimalsCell DifferentiationChick EmbryoGene Expression Regulation, DevelopmentalNeural TubeChickCRISPR/cas9In vivo screenNeural inductionNMPsSuper elongation complex

Identifiers

PMID39804120

DOI10.1242/dev.204591

PMCPMC11883246

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.