This web page was produced as an assignment for Genetics 677, an undergraduate course at UW-Madison.
Phenotypes
Fly Phenotypes
The Fgfr2 homolog in Drosophilia melanogaster, breathless, btl is also well studied. The simple structure of the fly respiratory system make it a great model for studying certain molecular mechanisms like cell migration. In multicellular organisms directed cell migration is often crucial for the correct development of many organs and tissues. Fly tracheal development and the directed cell migration involved have, as a result, become a common area of study (3).
Trachea
In this image the wild-type fly, photo A, shows normal migration and development of the tracheal system. Photos B and C, which represent a btl deletion and btl null allele respectively, show failed tracheal migration (3).
Mouse Phenotypes
The Fgfr2 gene and protein are best studied in mouse. Although homologs exist for at least 5 other species, most of the research in this field focuses on mice. As a model organism mice are much easier to work with than some the larger species with homologs, and more closely related to humans than non-mammalian species with homologs. The images below show some of the phenotypes found when the Fgfr2 gene is mutated in mouse models.
Head and SkullThese images display some of the results of a mutations in the Fgfr2 gene in the head and the skull compared to those in a wild-type mouse. Again, the wild-type images lay furthest to the left (A,D). The images on the right correspond to a mutation in the Fgfr2 gene that produces a similar phenotype to that seen in humans with Crouzon Syndrome. Image B, compared to image A, displays the protruding eyes and shortened face of the mutant while images D and E compare the wild-type skull's open sutures (noted by the arrows) to those completely fused in the mutant. These mutant phenotypes parallel those seen in human Crouzon patients (1).
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TracheaIn the above photo the cartilage of a mouse trachea is highlighted in red. Photo D shows normal development in the wild-type trachea where the cartilage is formed in rings. The other photos show the disruption in cartilage formation in two separate Fgfr2 mutations where a single sheath of cartilage is produced instead of rings (1).
LungsThis image shows a wild-type set of lungs complete with all lobes on the left. On the right, one can see the lungs are missing at two lobes due to a mutation in the Fgfr2 gene (2).
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Analysis
Although RNAi phenotypes have not been applied to this gene yet, these mutations have produced extremely helpful phenotypes to understanding Crouzon Syndrome and related diseases. Because Crouzon syndrome can be result of more than one different mutations, it will be important in the future to recreate the Crouzon phenotype in several types of mutations.
[1] V. P. Eswarakumar, F. Özcan, E. D. Lew, J. H. Bae, F. Tomé, C. J. Booth, D. J. Adams, I. Lax, and J. Schlessinger. Attenuation of signaling pathways stimulated by pathologically activated FGF-receptor 2 mutants prevents craniosynostosis. PNAS online. 2006.
PMID: 17132737
[2] Hajihosseini MK, Wilson S, De Moerlooze L, Dickson C. A splicing switch and gain-of-function mutation in FgfR2-IIIc hemizygotes causes Apert/Pfeiffer-syndrome-like phenotypes. PNAS - Developmental Biology. 2006.
PMID: 11274405
[3] Myat MM, Lightfoot H, Wang P, Andrew DJ. A molecular link between FGF and Dpp signaling in branch-specific migration of the Drosophila trachea. Dev Biol. 2005 May 1;281(1):38-52.
PMID: 15848387
PMID: 17132737
[2] Hajihosseini MK, Wilson S, De Moerlooze L, Dickson C. A splicing switch and gain-of-function mutation in FgfR2-IIIc hemizygotes causes Apert/Pfeiffer-syndrome-like phenotypes. PNAS - Developmental Biology. 2006.
PMID: 11274405
[3] Myat MM, Lightfoot H, Wang P, Andrew DJ. A molecular link between FGF and Dpp signaling in branch-specific migration of the Drosophila trachea. Dev Biol. 2005 May 1;281(1):38-52.
PMID: 15848387