PMID:10964473

Citation	Paine-Saunders, S, Viviano, BL, Zupicich, J, Skarnes, WC and Saunders, S (2000) glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development. Dev. Biol. 225:179-87
Abstract	Glypicans represent a family of six cell surface heparan sulfate proteoglycans in vertebrates. Although no specific in vivo functions have thus far been described for these proteoglycans, spontaneous mutations in the human and induced deletions in the mouse glypican-3 (Gpc3) gene result in severe malformations and both pre- and postnatal overgrowth, known clinically as the Simpson-Golabi-Behmel syndrome (SGBS). Mice carrying mutant alleles of Gpc3 created by either targeted gene disruption or gene trapping display a wide range of phenotypes associated with SGBS including renal cystic dysplasia, ventral wall defects, and skeletal abnormalities that are consistent with the pattern of Gpc3 expression in the mouse embryo. Previous studies in Drosophila have implicated glypicans in the signaling of decapentaplegic, a BMP homolog. Our experiments with mice show a significant relationship between vertebrate BMP signaling and glypican function; GPC3-deficient animals were mated with mice haploinsufficient for bone morphogenetic protein-4 (Bmp4) and their offspring displayed a high penetrance of postaxial polydactyly and rib malformations not observed in either parent strain. This previously unknown link between glypican-3 and BMP4 function provides evidence of a role for glypicans in vertebrate limb patterning and skeletal development and suggests a mechanism for the skeletal defects seen in SGBS.
Links	PubMed Online version:10.1006/dbio.2000.9831
Keywords	Animals; Body Patterning/physiology; Bone Development/physiology; Cell Differentiation; Embryonic and Fetal Development; Extremities/embryology; Extremities/physiology; Gene Expression Regulation, Developmental; Glypicans; Heparan Sulfate Proteoglycans/physiology; Humans; Mice; Mice, Inbred C57BL
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:BMP4	involved_in	GO:0009948: anterior/posterior axis specification	ECO:0000316: genetic interaction evidence used in manual assertion	MGI:MGI:104903	P		Seeded From UniProt	complete
MOUSE:BMP4	involved_in	GO:0035116: embryonic hindlimb morphogenesis	ECO:0000316: genetic interaction evidence used in manual assertion	MGI:MGI:104903	P		Seeded From UniProt	complete
MOUSE:GPC3	involved_in	GO:0009948: anterior/posterior axis specification	ECO:0000316: genetic interaction evidence used in manual assertion	MGI:MGI:88180	P		Seeded From UniProt	complete
MOUSE:GPC3	involved_in	GO:0035116: embryonic hindlimb morphogenesis	ECO:0000316: genetic interaction evidence used in manual assertion	MGI:MGI:88180	P		Seeded From UniProt	complete
MOUSE:BMP4	acts_upstream_of_or_within	GO:0009948: anterior/posterior axis specification	ECO:0000316: genetic interaction evidence used in manual assertion	MGI:MGI:104903	P		Seeded From UniProt	complete
MOUSE:BMP4	acts_upstream_of_or_within	GO:0035116: embryonic hindlimb morphogenesis	ECO:0000316: genetic interaction evidence used in manual assertion	MGI:MGI:104903	P	results_in_development_of:(EMAPA:17458)	Seeded From UniProt	complete

References

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