title: Bmp4 in limb bud mesoderm regulates digit pattern by controlling AER development.
abstract: In the developing limb, Bmp4 is expressed in the apical ectodermal ridge (AER) and underlying mesoderm. Insight into the function of Bmp4 in limb development has been hampered by the early embryonic lethality of Bmp4 null embryos. We directly investigated Bmp4 using a conditional null allele of Bmp4 and the Prx1(cre) transgene to inactivate Bmp4 in limb bud mesoderm. The limb bud mesoderm of Prx1(cre);Bmp4 mutants was defective in production of Bmp4 but still competent to respond to Bmp signaling. Prx1(cre);Bmp4 mutant embryos had defective digit patterning including hindlimb preaxial polydactyly with posterior digit transformations. The Prx1(cre);Bmp4 mutants also had postaxial polydactyly with digit five duplications. Bmp4 mutant limbs had delayed induction and maturation of the AER that resulted in expanded Shh signaling. Moreover, the AER persisted longer in the Bmp4 mutant limb buds exposing the forming digits to prolonged Fgf8 signaling. Our data show that Bmp4 in limb mesoderm regulates AER induction and maturation and implicate signaling from the AER in regulation of digit number and identity.
authors.affiliation: Alkek Institute of Biosciences and Technology, Texas A&M System Health Science Center, Houston, TX 77030, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Selever
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Mei-Fang
authors.initials: MF
authors.lastname: Lu
authors.forename: Richard R
authors.initials: RR
authors.lastname: Behringer
authors.forename: James F
authors.initials: JF
authors.lastname: Martin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning; D055415:Bone Morphogenetic Protein 4; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D004475:Ectoderm / Q000502:physiology*; D004622:Embryo, Mammalian / Q000033:anatomy & histology; D004627:Embryonic Induction; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D018878:Limb Buds / Q000002:abnormalities / Q000033:anatomy & histology* / Q000254:growth & development / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009024:Morphogenesis; D010641:Phenotype; D017689:Polydactyly / Q000235:genetics; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014034:Toes / Q000002:abnormalities / Q000033:anatomy & histology / Q000254:growth & development*; D019076:Transgenes
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018398:Homeodomain Proteins; C489936:Prrx1 protein, mouse; D017978:Receptors, Growth Factor; D017346:Protein Serine-Threonine Kinases; D052005:Bone Morphogenetic Protein Receptors, Type I