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Geminin prevents DNA damage in vagal neural crest cells to ensure normal enteric neurogenesis

Overview of attention for article published in BMC Biology, October 2016
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Title
Geminin prevents DNA damage in vagal neural crest cells to ensure normal enteric neurogenesis
Published in
BMC Biology, October 2016
DOI 10.1186/s12915-016-0314-x
Pubmed ID
Authors

Chrysoula Konstantinidou, Stavros Taraviras, Vassilis Pachnis

Abstract

In vertebrate organisms, the neural crest (NC) gives rise to multipotential and highly migratory progenitors which are distributed throughout the embryo and generate, among other structures, the peripheral nervous system, including the intrinsic neuroglial networks of the gut, i.e. the enteric nervous system (ENS). The majority of enteric neurons and glia originate from vagal NC-derived progenitors which invade the foregut mesenchyme and migrate rostro-caudally to colonise the entire length of the gut. Although the migratory behaviour of NC cells has been studied extensively, it remains unclear how their properties and response to microenvironment change as they navigate through complex cellular terrains to reach their target embryonic sites. Using conditional gene inactivation in mice we demonstrate here that the cell cycle-dependent protein Geminin (Gem) is critical for the survival of ENS progenitors in a stage-dependent manner. Gem deletion in early ENS progenitors (prior to foregut invasion) resulted in cell-autonomous activation of DNA damage response and p53-dependent apoptosis, leading to severe intestinal aganglionosis. In contrast, ablation of Gem shortly after ENS progenitors had invaded the embryonic gut did not result in discernible survival or migratory deficits. In contrast to other developmental systems, we obtained no evidence for a role of Gem in commitment or differentiation of ENS lineages. The stage-dependent resistance of ENS progenitors to mutation-induced genotoxic stress was further supported by the enhanced survival of post gut invasion ENS lineages to γ-irradiation relative to their predecessors. Our experiments demonstrate that, in mammals, NC-derived ENS lineages are sensitive to genotoxic stress in a stage-specific manner. Following gut invasion, ENS progenitors are distinctly resistant to Gem ablation and irradiation in comparison to their pre-enteric counterparts. These studies suggest that the microenvironment of the embryonic gut protects ENS progenitors and their progeny from genotoxic stress.

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 6%
France 1 6%
Unknown 15 88%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 24%
Researcher 3 18%
Student > Master 3 18%
Lecturer > Senior Lecturer 1 6%
Other 1 6%
Other 1 6%
Unknown 4 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 3 18%
Agricultural and Biological Sciences 3 18%
Neuroscience 3 18%
Medicine and Dentistry 3 18%
Design 1 6%
Other 0 0%
Unknown 4 24%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 23 December 2016.
All research outputs
#7,951,978
of 12,680,068 outputs
Outputs from BMC Biology
#966
of 1,138 outputs
Outputs of similar age
#160,600
of 286,135 outputs
Outputs of similar age from BMC Biology
#96
of 115 outputs
Altmetric has tracked 12,680,068 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,138 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.3. This one is in the 9th percentile – i.e., 9% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 286,135 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 115 others from the same source and published within six weeks on either side of this one. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.