title: Stability and plasticity of neural crest patterning and branchial arch Hox code after extensive cephalic crest rotation.
abstract: The extent to which the spatial organisation of craniofacial development is due to intrinsic properties of the neural crest is at present unclear. There is some experimental evidence supporting the concept of a prepattern established within crest while contiguous with the neural plate. In experiments in which the neural tube and premigratory crest are relocated within the branchial region, crest cells retain patterns of gene expression appropriate for their position of origin after migration into the branchial arches, resulting in skeletal abnormalities. But in apparent conflict with these findings, when crest is rerouted by late deletion of adjacent crest, infilling crest alters its pattern of gene expression to match its new location, and a normal facial skeleton results. In order to reconcile these findings thus identify processes of relevance to the course of normal development, we have performed a series of neural tube and crest rotations producing a more extensive reorganisation of cephalic crest than has been previously described. Lineage analysis using DiI labelling of crest derived from the rotated hindbrain reveals that crest does not migrate into the branchial arch it would have colonised in normal development, rather it simply populates the nearest available branchial arches. We also find that crest adjacent to the grafted region contributes to a greater number of branchial arches than it would in normal development, resulting in branchial arches containing mixed cell populations not occurring in normal development. We find that after exchange of first and third arch crest by rotation of r1-7, crest alters its expression of hoxa-2 and hoxa-3 to match its new location within the embryo resulting in the reestablishment of the normal branchial arch Hox code. A facial skeleton in which all the normal components are present, with some additional ectopic first arch structures, is formed in this situation. In contrast, when second and third arch crest are exchanged by rotation of r3 to 7, ectopic Hox gene expression is stable, resulting in the persistence of an abnormal branchial arch Hox code and extensive defects in the hyoid skeleton. We suggest that the intrinsic properties of crest have an effect on the spatial organisation of structures derived from the branchial arches, but that exposure to increasingly novel environments within the branchial region or "community effects" within mixed populations of cells can result in alterations to crest Hox code and morphogenetic fate. In both classes of operation we find that there is a tight link between the resulting branchial arch Hox code and a particular skeletal morphology.
authors.affiliation: Developmental Biology Unit, Institute of Child Health, London, United Kingdom. P.N.Hunt@durham.ac.uk
authors.forename: P
authors.initials: P
authors.lastname: Hunt
authors.forename: J D
authors.initials: JD
authors.lastname: Clarke
authors.forename: P
authors.initials: P
authors.lastname: Buxton
authors.forename: P
authors.initials: P
authors.lastname: Ferretti
authors.forename: P
authors.initials: P
authors.lastname: Thorogood
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D002642:Chick Embryo; D005456:Fluorescent Dyes / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006651:Histocytochemistry; D018398:Homeodomain Proteins / Q000378:metabolism; D008445:Maxillofacial Development / Q000502:physiology*; D008648:Mesoderm / Q000502:physiology; D009024:Morphogenesis / Q000502:physiology; D009432:Neural Crest / Q000254:growth & development*; D016378:Tissue Transplantation
chemical_list: D005456:Fluorescent Dyes; D018398:Homeodomain Proteins