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later stages of limb development, BMP activity is also believed to play critical roles in skeletogenesis. Activation and dominant-negative experiments in the chick have shown that signaling through the BMPR-IB receptor is necessary and sufficient for cartilage condensation in chick [25]. Likewise, conditional knockout of BmpR1A and BmpR1B blocks all chondrogenic differentiation in the mouse limb bud [26]. Similarly, when noggin, a potent BMP inhibitor, is introduced in early stage chick limb buds prior to skeletogenesis, mesenchymal condensation does not take place [27,28]. Taken together, these studies strongly implicate BMP signaling as necessary for mesenchymal condensations and the initiation of chondrogenesis. However, the phenotypes in these experiments are severe, causing either global chondrogenesis or absence of chondrogenesis, in the gain- and loss-of-function experiments, respectively. These severe defects during the early stages of skeletogenesis preclude investigation of any specific roles for BMPs in later events in cartilage differentiation, bone formation, and bone metabolism [29]. Conversely, removal of individual ligands such as BMP4 [16] or BMP7 [12,13] has not displayed defects in skeletal differentiation, presumably due to functional redundancy."}

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{"project":"2_test","denotations":[{"id":"17194222-9303535-85946845","span":{"begin":287,"end":289},"obj":"9303535"},{"id":"17194222-15781876-85946846","span":{"begin":407,"end":409},"obj":"15781876"},{"id":"17194222-9630747-85946847","span":{"begin":576,"end":578},"obj":"9630747"},{"id":"17194222-10694419-85946848","span":{"begin":579,"end":581},"obj":"10694419"},{"id":"17194222-11970890-85946849","span":{"begin":1113,"end":1115},"obj":"11970890"},{"id":"17194222-15581864-85946850","span":{"begin":1174,"end":1176},"obj":"15581864"},{"id":"17194222-7590254-85946851","span":{"begin":1187,"end":1189},"obj":"7590254"},{"id":"17194222-7590255-85946852","span":{"begin":1190,"end":1192},"obj":"7590255"},{"id":"T80151","span":{"begin":287,"end":289},"obj":"9303535"},{"id":"T89250","span":{"begin":407,"end":409},"obj":"15781876"},{"id":"T52744","span":{"begin":576,"end":578},"obj":"9630747"},{"id":"T12763","span":{"begin":579,"end":581},"obj":"10694419"},{"id":"T10676","span":{"begin":1113,"end":1115},"obj":"11970890"},{"id":"T95280","span":{"begin":1174,"end":1176},"obj":"15581864"},{"id":"T19072","span":{"begin":1187,"end":1189},"obj":"7590254"},{"id":"T37769","span":{"begin":1190,"end":1192},"obj":"7590255"}],"text":"At later stages of limb development, BMP activity is also believed to play critical roles in skeletogenesis. Activation and dominant-negative experiments in the chick have shown that signaling through the BMPR-IB receptor is necessary and sufficient for cartilage condensation in chick [25]. Likewise, conditional knockout of BmpR1A and BmpR1B blocks all chondrogenic differentiation in the mouse limb bud [26]. Similarly, when noggin, a potent BMP inhibitor, is introduced in early stage chick limb buds prior to skeletogenesis, mesenchymal condensation does not take place [27,28]. Taken together, these studies strongly implicate BMP signaling as necessary for mesenchymal condensations and the initiation of chondrogenesis. However, the phenotypes in these experiments are severe, causing either global chondrogenesis or absence of chondrogenesis, in the gain- and loss-of-function experiments, respectively. These severe defects during the early stages of skeletogenesis preclude investigation of any specific roles for BMPs in later events in cartilage differentiation, bone formation, and bone metabolism [29]. Conversely, removal of individual ligands such as BMP4 [16] or BMP7 [12,13] has not displayed defects in skeletal differentiation, presumably due to functional redundancy."}

{"project":"craft-ca-core-dev","denotations":[{"id":"T744","span":{"begin":19,"end":23},"obj":"UBERON:0002101"},{"id":"T745","span":{"begin":19,"end":35},"obj":"GO:0060173"},{"id":"T746","span":{"begin":37,"end":40},"obj":"PR:000000034"},{"id":"T747","span":{"begin":93,"end":107},"obj":"GO:0001501"},{"id":"T748","span":{"begin":205,"end":221},"obj":"PR:000000036"},{"id":"T749","span":{"begin":254,"end":276},"obj":"GO:0001502"},{"id":"T750","span":{"begin":326,"end":332},"obj":"PR:000000035"},{"id":"T751","span":{"begin":337,"end":343},"obj":"PR:000000036"},{"id":"T752","span":{"begin":355,"end":367},"obj":"GO:0051216"},{"id":"T753","span":{"begin":391,"end":396},"obj":"NCBITaxon:10088"},{"id":"T754","span":{"begin":397,"end":405},"obj":"UBERON:0004347"},{"id":"T755","span":{"begin":428,"end":434},"obj":"PR:000000021"},{"id":"T756","span":{"begin":445,"end":448},"obj":"PR:000000034"},{"id":"T757","span":{"begin":449,"end":458},"obj":"CHEBI:35222"},{"id":"T758","span":{"begin":495,"end":504},"obj":"UBERON:0004347"},{"id":"T759","span":{"begin":514,"end":528},"obj":"GO:0001501"},{"id":"T760","span":{"begin":530,"end":541},"obj":"UBERON:0003104"},{"id":"T761","span":{"begin":633,"end":636},"obj":"PR:000000034"},{"id":"T762","span":{"begin":633,"end":646},"obj":"GO:0030509"},{"id":"T763","span":{"begin":664,"end":675},"obj":"UBERON:0003104"},{"id":"T764","span":{"begin":712,"end":726},"obj":"GO:0051216"},{"id":"T765","span":{"begin":807,"end":821},"obj":"GO:0051216"},{"id":"T766","span":{"begin":836,"end":850},"obj":"GO:0051216"},{"id":"T767","span":{"begin":961,"end":975},"obj":"GO:0001501"},{"id":"T768","span":{"begin":1025,"end":1029},"obj":"PR:000000034"},{"id":"T769","span":{"begin":1101,"end":1111},"obj":"GO:0008152"},{"id":"T770","span":{"begin":1168,"end":1172},"obj":"PR:000000165"},{"id":"T771","span":{"begin":1181,"end":1185},"obj":"PR:000000168"},{"id":"T772","span":{"begin":1223,"end":1231},"obj":"UBERON:0004288"}],"text":"At later stages of limb development, BMP activity is also believed to play critical roles in skeletogenesis. Activation and dominant-negative experiments in the chick have shown that signaling through the BMPR-IB receptor is necessary and sufficient for cartilage condensation in chick [25]. Likewise, conditional knockout of BmpR1A and BmpR1B blocks all chondrogenic differentiation in the mouse limb bud [26]. Similarly, when noggin, a potent BMP inhibitor, is introduced in early stage chick limb buds prior to skeletogenesis, mesenchymal condensation does not take place [27,28]. Taken together, these studies strongly implicate BMP signaling as necessary for mesenchymal condensations and the initiation of chondrogenesis. However, the phenotypes in these experiments are severe, causing either global chondrogenesis or absence of chondrogenesis, in the gain- and loss-of-function experiments, respectively. These severe defects during the early stages of skeletogenesis preclude investigation of any specific roles for BMPs in later events in cartilage differentiation, bone formation, and bone metabolism [29]. Conversely, removal of individual ligands such as BMP4 [16] or BMP7 [12,13] has not displayed defects in skeletal differentiation, presumably due to functional redundancy."}