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Vascular patterning regulates interdigital cell death by a ROS-mediated mechanism
- Source :
- Development.
- Publication Year :
- 2015
- Publisher :
- The Company of Biologists, 2015.
-
Abstract
- Blood vessels serve as key regulators of organogenesis by providing oxygen, nutrients and molecular signals. During limb development, programmed cell death (PCD) contributes to separation of the digits. Interestingly, prior to the onset of PCD, the autopod vasculature undergoes extensive patterning that results in high interdigital vascularity. Here, we show that in mice, the limb vasculature positively regulates interdigital PCD. In vivo, reduction in interdigital vessel number inhibited PCD, resulting in syndactyly, whereas an increment in vessel number and distribution resulted in elevation and expansion of PCD. Production of reactive oxygen species (ROS), toxic compounds that have been implicated in PCD, also depended on interdigital vascular patterning. Finally, ex vivo incubation of limbs in gradually decreasing oxygen levels led to a correlated reduction in both ROS production and interdigital PCD. The results support a role for oxygen in these processes and provide a mechanistic explanation for the counterintuitive positive role of the vasculature in PCD. In conclusion, we suggest a new role for vascular patterning during limb development in regulating interdigital PCD by ROS production. More broadly, we propose a double safety mechanism that restricts PCD to interdigital areas, as the genetic program of PCD provides the first layer and vascular patterning serves as the second.
- Subjects :
- Programmed cell death
animal structures
Vascular patterning
Organogenesis
Biology
Mice
Organ Culture Techniques
Pregnancy
In vivo
otorhinolaryngologic diseases
Animals
Limb development
Molecular Biology
chemistry.chemical_classification
Reactive oxygen species
Cell Death
Gene Expression Regulation, Developmental
Extremities
Limb vasculature
Anatomy
respiratory tract diseases
Cell biology
chemistry
Female
Reactive Oxygen Species
Ex vivo
Developmental Biology
Subjects
Details
- ISSN :
- 14779129 and 09501991
- Database :
- OpenAIRE
- Journal :
- Development
- Accession number :
- edsair.doi.dedup.....e52f37d98e884fc503791fd060a40351
- Full Text :
- https://doi.org/10.1242/dev.120279