title: Fgf8 dosage determines midfacial integration and polarity within the nasal and optic capsules.
abstract: Craniofacial development requires an exquisitely timed and positioned cross-talk between the embryonic cephalic epithelia and mesenchyme. This cross-talk underlies the precise translation of patterning processes and information into distinct, appropriate skeletal morphologies. The molecular and cellular dialogue includes communication via secreted signaling molecules, including Fgf8, and effectors of their interpretation. Herein, we use genetic attenuation of Fgf8 in mice and perform gain-of-function mouse-chick chimeric experiments to demonstrate that significant character states of the frontonasal and optic skeletons are dependent on Fgf8. Notably, we show that the normal orientation and polarity of the nasal capsules and their developing primordia are dependent on Fgf8. We further demonstrate that Fgf8 is required for midfacial integration, and provide evidence for a role for Fgf8 in optic capsular development. Taken together, our data highlight Fgf8 signaling in craniofacial development as a plausible target for evolutionary selective pressures.
authors.affiliation: Dept. of Craniofacial Development, King's College London, Floor 27, Guy's Hospital, London Bridge, London SE1 9RT, UK.
authors.forename: John N
authors.initials: JN
authors.lastname: Griffin
authors.forename: Claudia
authors.initials: C
authors.lastname: Compagnucci
authors.forename: Diane
authors.initials: D
authors.lastname: Hu
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fish
authors.forename: Ophir
authors.initials: O
authors.lastname: Klein
authors.forename: Ralph
authors.initials: R
authors.lastname: Marcucio
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Depew
mesh_terms: D000483:Alleles; D000818:Animals; D049109:Cell Proliferation; D002642:Chick Embryo; D004475:Ectoderm / Q000378:metabolism; D005123:Eye / Q000196:embryology* / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D020287:In Situ Nick-End Labeling; D051379:Mice; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008954:Models, Biological; D009297:Nasal Mucosa / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: C496457:Fgf8 protein, mouse; D051524:Fibroblast Growth Factor 8