title: A staging system for correct phenotype interpretation of mouse embryos harvested on embryonic day 14 (E14.5).
abstract: We present a simple and quick system for accurately scoring the developmental progress of mouse embryos harvested on embryonic day 14 (E14.5). Based solely on the external appearance of the maturing forelimb, we provide a convenient way to distinguish six developmental sub-stages. Using a variety of objective morphometric data obtained from the commonly used C57BL/6N mouse strain, we show that these stages correlate precisely with the growth of the entire embryo and its organs. Applying the new staging system to phenotype analyses of E14.5 embryos of 58 embryonic lethal null mutant lines from the DMDD research programme (https://dmdd.org.uk) and its pilot, we show that homozygous mutant embryos are frequently delayed in development. To demonstrate the importance of our staging system for correct phenotype interpretation, we describe stage-specific changes of the palate, heart and gut, and provide examples in which correct diagnosis of malformations relies on correct staging.
authors.affiliation: Centre for Anatomy and Cell Biology & MIC, Medical University of Vienna, Vienna, Austria.
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Geyer
authors.affiliation: Centre for Anatomy and Cell Biology & MIC, Medical University of Vienna, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Reissig
authors.affiliation: Centre for Anatomy and Cell Biology & MIC, Medical University of Vienna, Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Rose
authors.affiliation: The Francis Crick Institute Mill Hill Laboratory, London, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Wilson
authors.affiliation: The Francis Crick Institute Mill Hill Laboratory, London, UK.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Prin
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, UK.
authors.forename: Dorota
authors.initials: D
authors.lastname: Szumska
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Ramirez-Solis
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Tudor
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
authors.forename: Jacqui
authors.initials: J
authors.lastname: White
authors.affiliation: The Francis Crick Institute Mill Hill Laboratory, London, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Mohun
authors.affiliation: Centre for Anatomy and Cell Biology & MIC, Medical University of Vienna, Vienna, Austria.
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Weninger
mesh_terms: D000818:Animals; D047108:Embryonic Development / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D010641:Phenotype; D013045:Species Specificity
keywords: Deciphering the Mechanisms of Developmental Disorders; embryo; high-resolution episcopic microscopy; knock out; morphology; mutant