title: 3D modelling, gene expression mapping and post-mapping image analysis in the developing human brain.
abstract: As human brain development proceeds, there are complex changes in size and shape, most notably in the developing forebrain. Molecular technologies enable us to characterise the gene expression patterns that underlie these changes. To interpret these patterns the location of expression must be identified and, often, gene expression patterns compared for several genes or across several developmental stages. To facilitate interpretation we have generated a set of three-dimensional models using a recently developed technique, optical projection tomography. The models act as a framework onto which gene expression patterns are mapped and anatomical domains identified using custom-designed software, MAPaint. Here, we demonstrate their use to compare forebrain development at two embryonic stages (Carnegie stages 18 and 21; 44 and 52 days post conception, respectively) and as a means of recording, storing and visualising gene expression data for three example genes EMX1, EMX2 and OTX2. Anatomical domains were also mapped to the models and the comparison of gene expression and anatomical data is demonstrated at Carnegie stage 21. The three-dimensional models and sophisticated software facilitate the analysis and visualisation of morphological changes and gene expression patterns during early brain development and can be applied to the development of other complex structures.
authors.affiliation: Institute of Human Genetics, University of Newcastle, Central Parkway, UK.
authors.forename: Subrot
authors.initials: S
authors.lastname: Sarma
authors.forename: Janet
authors.initials: J
authors.lastname: Kerwin
authors.forename: Luis
authors.initials: L
authors.lastname: Puelles
authors.forename: Mark
authors.initials: M
authors.lastname: Scott
authors.forename: Tom
authors.initials: T
authors.lastname: Strachan
authors.forename: Guangjie
authors.initials: G
authors.lastname: Feng
authors.forename: James
authors.initials: J
authors.lastname: Sharpe
authors.forename: Duncan
authors.initials: D
authors.lastname: Davidson
authors.forename: Richard
authors.initials: R
authors.lastname: Baldock
authors.forename: Susan
authors.initials: S
authors.lastname: Lindsay
mesh_terms: D001921:Brain / Q000196:embryology / Q000378:metabolism*; D001931:Brain Mapping; D002874:Chromosome Mapping; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D021621:Imaging, Three-Dimensional / Q000379:methods; D056892:Mediator Complex; D008953:Models, Anatomic; D051857:Otx Transcription Factors / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D018398:Homeodomain Proteins; D056892:Mediator Complex; D051857:Otx Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C492160:MED14 protein, human; C497659:OTX2 protein, human