@article{
 title = {BMPs are direct triggers of interdigital programmed cell death},
 type = {article},
 year = {2016},
 pages = {266-276},
 id = {15eb1aab-629a-3e82-a138-1a5dfccd34eb},
 created = {2016-04-28T07:16:53.000Z},
 file_attached = {true},
 profile_id = {c74c621a-34b4-35a7-9ea5-041719220e9f},
 group_id = {cec5aa9e-65e1-3c21-bc44-78fa6504020e},
 last_modified = {2017-03-14T10:42:46.538Z},
 read = {false},
 starred = {false},
 authored = {false},
 confirmed = {false},
 hidden = {false},
 folder_uuids = {42bb573e-c5b5-4afd-9bdb-2e9023c04e10},
 private_publication = {false},
 abstract = {During vertebrate embryogenesis the interdigital mesenchyme is removed by programmed cell death
(PCD), except in species with webbed limbs. Although bone morphogenetic proteins (BMPs) have long been known to be players in this process, it is unclear if they play a direct role in the interdigital me-
senchyme or if they only act indirectly, by affecting
fibroblast growth factor (FGF) signaling. A series of
genetic studies have shown that BMPs act indirectly by regulating the withdrawal of FGF activity from
the apical ectodermal ridge (AER); this FGF activity acts as a cell survival factor for the underlying me-
senchyme. Other studies using exogenous factors to inhibit BMP activity in explanted mouse limbs
suggest that BMPs do not act directly in the mesenchyme. To address the question of whether BMPs act directly, we used an interdigit-specific Cre line to inactivate several genes that encode components of the BMP signaling pathway, without perturbing the normal downregulation of AER-FGF activity. Of three Bmps expressed in the interdigital mesenchyme, Bmp7 is necessary for PCD, but Bmp2 and Bmp4 both have redundant roles, with Bmp2 being the more prominent player. Removing BMP signals to the interdigit by deleting the receptor gene, Bmpr1a, causes a loss of PCD and syndactyly, thereby unequivocally proving that BMPs are direct triggers of PCD in this tissue. We present a model in which two
events must occur for normal interdigital PCD: the presence of a BMP death trigger and the absence of an FGF survival activity. We demonstrate that neither event is required for formation of the interdigital vasculature, which is necessary for PCD. However, both events converge on the production of reactive
oxygen species that activate PCD.},
 bibtype = {article},
 author = {Maria M. Kaltcheva, undefined and Matthew J. Anderson, undefined and Brian D. Harfe, undefined and Mark Lewandoski, undefined},
 journal = {Developmental Biology}
}

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Although bone morphogenetic proteins (BMPs) have long been known to be players in this process, it is unclear if they play a direct role in the interdigital me-\r\nsenchyme or if they only act indirectly, by affecting\r\nfibroblast growth factor (FGF) signaling. A series of\r\ngenetic studies have shown that BMPs act indirectly by regulating the withdrawal of FGF activity from\r\nthe apical ectodermal ridge (AER); this FGF activity acts as a cell survival factor for the underlying me-\r\nsenchyme. Other studies using exogenous factors to inhibit BMP activity in explanted mouse limbs\r\nsuggest that BMPs do not act directly in the mesenchyme. To address the question of whether BMPs act directly, we used an interdigit-specific Cre line to inactivate several genes that encode components of the BMP signaling pathway, without perturbing the normal downregulation of AER-FGF activity. Of three Bmps expressed in the interdigital mesenchyme, Bmp7 is necessary for PCD, but Bmp2 and Bmp4 both have redundant roles, with Bmp2 being the more prominent player. Removing BMP signals to the interdigit by deleting the receptor gene, Bmpr1a, causes a loss of PCD and syndactyly, thereby unequivocally proving that BMPs are direct triggers of PCD in this tissue. We present a model in which two\r\nevents must occur for normal interdigital PCD: the presence of a BMP death trigger and the absence of an FGF survival activity. We demonstrate that neither event is required for formation of the interdigital vasculature, which is necessary for PCD. However, both events converge on the production of reactive\r\noxygen species that activate PCD.","bibtype":"article","author":"Maria M. Kaltcheva, undefined and Matthew J. Anderson, undefined and Brian D. 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Although bone morphogenetic proteins (BMPs) have long been known to be players in this process, it is unclear if they play a direct role in the interdigital me-\r\nsenchyme or if they only act indirectly, by affecting\r\nfibroblast growth factor (FGF) signaling. A series of\r\ngenetic studies have shown that BMPs act indirectly by regulating the withdrawal of FGF activity from\r\nthe apical ectodermal ridge (AER); this FGF activity acts as a cell survival factor for the underlying me-\r\nsenchyme. Other studies using exogenous factors to inhibit BMP activity in explanted mouse limbs\r\nsuggest that BMPs do not act directly in the mesenchyme. To address the question of whether BMPs act directly, we used an interdigit-specific Cre line to inactivate several genes that encode components of the BMP signaling pathway, without perturbing the normal downregulation of AER-FGF activity. Of three Bmps expressed in the interdigital mesenchyme, Bmp7 is necessary for PCD, but Bmp2 and Bmp4 both have redundant roles, with Bmp2 being the more prominent player. Removing BMP signals to the interdigit by deleting the receptor gene, Bmpr1a, causes a loss of PCD and syndactyly, thereby unequivocally proving that BMPs are direct triggers of PCD in this tissue. We present a model in which two\r\nevents must occur for normal interdigital PCD: the presence of a BMP death trigger and the absence of an FGF survival activity. We demonstrate that neither event is required for formation of the interdigital vasculature, which is necessary for PCD. However, both events converge on the production of reactive\r\noxygen species that activate PCD.},\n bibtype = {article},\n author = {Maria M. Kaltcheva, undefined and Matthew J. Anderson, undefined and Brian D. Harfe, undefined and Mark Lewandoski, undefined},\n journal = {Developmental Biology}\n}","author_short":["Maria M. 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