ArticleDevelopmental biology2016
BMPs are direct triggers of interdigital programmed cell death.
Article in Developmental biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Transient cartilages and interdigital vasculature organization in the embryonic duck foot.Royal Society open science · 2026Article
- Allele specific expression in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Molecular analysis of Aldh1a2 conditional inactivation in developing limbs reveals mechanisms of retinoic-acid mediated interdigital apoptosis.Frontiers in cell and developmental biology · 2026Article
- BMP-Dependent Modulation of ROS Generation and Scavenging Controls Interdigital Cell Death.Development, growth & differentiation · 2026Article
- POGLUT2/3 mediated EGF O-glucosylation promotes separation of digits 2 and 3 by influencing fibrillin network reorganization, signaling, and cell dynamics.Developmental biology · 2025Article
- Comparative single-cell analyses reveal evolutionary repurposing of a conserved gene programme in bat wing development.Nature ecology & evolution · 2025Article
- Article
- Transcriptome data from the interdigital webs of the Chinese Soft-shell Turtle (Pelodiscus sinensis).Scientific data · 2025Article
- A whole-body atlas of BMP signaling activity in an adult sea anemone.BMC biology · 2025Article
- Article
- Macrophages allocate before apoptosis initiation and produce reactive oxygen species during interdigital phagocytosis.Biology open · 2024Article
- Air-breathing behavior underlies the cell death in limbs of Rana pirica tadpoles.Zoological letters · 2023Article
- Article
- Evolutionary genetics of flipper forelimb and hindlimb loss from limb development-related genes in cetaceans.BMC genomics · 2022Article
- Loss of BMP2 and BMP4 Signaling in the Dental Epithelium Causes Defective Enamel Maturation and Aberrant Development of Ameloblasts.International journal of molecular sciences · 2022Article
- Genetic determinants of syndactyly: perspectives on pathogenesis and diagnosis.Orphanet journal of rare diseases · 2022Review
- Cell death in the developing vertebrate limb: A locally regulated mechanism contributing to musculoskeletal tissue morphogenesis and differentiation.Developmental dynamics : an official publication of the American Association of Anatomists · 2021Review
- Hoxd13/Bmp2-mediated mechanism involved in zebrafish finfold design.Scientific reports · 2021Article
- Regulation of the limb shape during the development of the Chinese softshell turtles.Evolution & development · 2020Article
- Epithelial Migration and Non-adhesive Periderm Are Required for Digit Separation during Mammalian Development.Developmental cell · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
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 mesenchyme 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 mesenchyme. 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.