title: In the limb AER Bmp2 and Bmp4 are required for dorsal-ventral patterning and interdigital cell death but not limb outgrowth.
abstract: The apical ectodermal ridge (AER) in the vertebrate limb is required for limb outgrowth and patterning. To investigate the role BMP ligands expressed in the AER play in limb development we selectively inactivated both Bmp2 and Bmp4 in this tissue. The autopods of mice lacking both of these genes contained extra digits, digit bifurcations and interdigital webbing due to a decrease in programmed cell death and an increase in cell proliferation in the underlying mesoderm. Upon removal of Bmp2 and Bmp4 in the AER, no defects in proximal-distal patterning were observed. At the molecular level, removal of Bmp2 and Bmp4 in the AER caused an increase in Fgf expression, which correlated with an increase in both the width and length of the AER. Investigation of Engrailed-1 (En1) expression in the AER of limb buds in which Bmp2 and Bmp4 had been removed indicated that En1 expression was absent from this tissue. Our data suggests that AER expression of Bmp2 and Bmp4 is required for digit and dorsal-ventral patterning but surprisingly not for limb outgrowth.
authors.affiliation: Department of Molecular Genetics and Microbiology and the Genetics Institute, University of Florida, College of Medicine, Gainesville, FL 32611, USA.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Maatouk
authors.forename: Kyung-Suk
authors.initials: KS
authors.lastname: Choi
authors.forename: Cortney M
authors.initials: CM
authors.lastname: Bouldin
authors.forename: Brian D
authors.initials: BD
authors.lastname: Harfe
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D049109:Cell Proliferation; D016207:Cytokines; D004475:Ectoderm / Q000033:anatomy & histology / Q000502:physiology; D005121:Extremities / Q000033:anatomy & histology / Q000196:embryology; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D017880:Limb Deformities, Congenital; D008297:Male; D051379:Mice; D015398:Signal Transduction / Q000502:physiology
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D016207:Cytokines; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C113178:Grem1 protein, mouse; C080330:En1 protein, mouse