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Cited by 600

The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.

Opposing actions of Arx and Pax4 in endocrine pancreas development

Open access
Collombat, Patrick, Mansouri, Ahmed, Hecksher-Sørensen, Jacob, Serup, Palle, Krull, Jens, Gradwohl, Gerard, Gruss, Peter·2003·Genes & Development

Abstract

Genes encoding homeodomain-containing proteins potentially involved in endocrine pancreas development were isolated by combined in silico and nested-PCR approaches. One such transcription factor, Arx, exhibits Ngn3-dependent expression throughout endocrine pancreas development in α, β-precursor, and δ cells. We have used gene targeting in mouse embryonic stem cells to generate Arx loss-of-function mice. Arx-deficient animals are born at the expected Mendelian frequency, but develop early-onset hypoglycemia, dehydration, and weakness, and die 2 d after birth. Immunohistological analysis of pancreas from Arx mutants reveals an early-onset loss of mature endocrine α cells with a concomitant increase in β-and δ-cell numbers, whereas islet morphology remains intact. Our study indicates a requirement of Arx for α-cell fate acquisition and a repressive action on β-and δ-cell destiny, which is exactly the opposite of the action of Pax4 in endocrine commitment. Using multiplex reverse transcriptase PCR (RT-PCR), we demonstrate an accumulation of Pax4 and Arx transcripts in Arx and Pax4 mutant mice, respectively. We propose that the antagonistic functions of Arx and Pax4 for proper islet cell specification are related to the pancreatic levels of the respective transcripts.

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Metadata

Authors
Collombat, P., Mansouri, A., Hecksher-Sørensen, J., Serup, P., Krull, J., Gradwohl, G., & Gruss, P.
Venue
Genes & Development
Published
2003-10-15
Volume
17
Issue
20
Pages
2591-2603
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W2110760195
Cited by
600
References
36
Type
posted content
Language
en
Open access
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CoChat. (2026). Citation check: Opposing actions of Arx and Pax4 in endocrine pancreas development. https://app.cochat.ai/papers/10.1101/gad.269003
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Collombat, P., Mansouri, A., Hecksher-Sørensen, J., Serup, P., Krull, J., Gradwohl, G., & Gruss, P. (2003). Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes & Development. https://doi.org/10.1101/gad.269003

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