Conditional mutation of fibroblast growth factor receptors 1 and 2 results in an omphalocele in mice associated with disruptions in ventral body wall muscle formation.
OBJECTIVE
We observed that fibroblast growth factor receptors 1 and 2 (Fgfr1, Fgfr2) are expressed during abdominal wall development in mice and hypothesized that conditional mutation of these genes would result in abdominal wall defects.


METHODS
Section in situ hybridizations were performed for Fgfr1 and Fgfr2 on wild-type embryos at embryonic day (E) 11.5 and E13.5. Conditional mutation of Fgfr1and Fgfr2 was achieved with a tamoxifen inducible Cre at E8.5. Litters were harvested at E17.5, whole mount photographs were taken, and paraffin sections were generated and stained with hematoxylin and eosin.


RESULTS
Fgfr1 was expressed in ectoderm, lateral plate mesoderm, and myoblasts, whereas Fgfr2 was expressed almost exclusively in the early dermis and ectoderm of the abdominal wall. Conditional mutation of both Fgfr2 alleles and one Fgfr1 allele resulted in omphalocele in 38.7% of mutants. Histologic examination in mutants demonstrated disruptions in dermal and muscle development.


CONCLUSIONS
Mutant embryos with omphalocele arising from mutation in Fgfr1 and Fgfr2 exhibit disruptions in the development of the secondary abdominal wall structures. These findings are consistent with a model of ventral abdominal wall development in which organization of the muscles and connective tissue (secondary abdominal wall structures) is influenced by positional information emanating from the primary abdominal wall.
University of Wisconsin School of Medicine and Public Health Department of Surgery, Madison, WI 53792, USA. nichol@surgery.wisc.edu
Peter F
PF
Nichol
Robert F
RF
Corliss
John D
JD
Tyrrell
Bradley
B
Graham
Amy
A
Reeder
Yukio
Y
Saijoh
D000009:Abdominal Muscles / Q000196:embryology / Q000254:growth & development; D034861:Abdominal Wall / Q000196:embryology* / Q000254:growth & development; D000818:Animals; D019521:Body Patterning / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006554:Hernia, Umbilical / Q000196:embryology / Q000235:genetics*; D051379:Mice; D009154:Mutation / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*
D017468:Receptors, Fibroblast Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2
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