Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage. - Archive ouverte HAL Access content directly
Journal Articles BMC Developmental Biology Year : 2011

Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage.

(1) , (2) , (1, 3) , (4)
1
2
3
4

Abstract

ABSTRACT: BACKGROUND: Nkx2.2 and Arx represent key transcription factors implicated in the specification of islet cell subtypes during pancreas development. Mice deficient for Arx do not develop any alpha-cells whereas beta- and delta-cells are found in considerably higher numbers. In Nkx2.2 mutant animals, alpha- and beta-cell development is severely impaired whereas a ghrelin-expressing cell population is found augmented. Notably, Arx transcription is clearly enhanced in Nkx2.2-deficient pancreata. Hence in order to precise the functional link between both factors we performed a comparative analysis of Nkx2.2/Arx single- and double-mutants but also of Pax6-deficient animals. RESULTS: We show that most of the ghrelin+ cells emerging in pancreata of Nkx2.2- and Pax6-deficient mice, express the alpha-cell specifier Arx, but also additional beta-cell related genes. In Nkx2.2-deficient mice, Arx directly co-localizes with iAPP, PC1/3 and Pdx1 suggesting an Nkx2.2-dependent control of Arx in committed beta-cells. The combined loss of Nkx2.2 and Arx likewise results in the formation of a hyperplastic ghrelin+ cell population at the expense of mature alpha- and beta-cells. Surprisingly, such Nkx2.2-/-Arx- ghrelin+ cells also express the somatostatin hormone. CONCLUSIONS: Our data indicate that Nkx2.2 acts by reinforcing the transcriptional networks initiated by Pax4 and Arx in early committed beta- and alpha-cell, respectively. Our analysis also suggests that one of the coupled functions of Nkx2.2 and Pax4 is to counteract Arx gene activity in early committed beta-cells.
Fichier principal
Vignette du fichier
1471-213X-11-52.pdf (2.22 Mo) Télécharger le fichier
Vignette du fichier
1471-213X-11-52.xml (102.18 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other

Dates and versions

inserm-00626327 , version 1 (25-09-2011)

Identifiers

Cite

Simon Kordowich, Patrick Collombat, Ahmed Mansouri, Palle Serup. Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineage.. BMC Developmental Biology, 2011, 11 (1), pp.52. ⟨10.1186/1471-213X-11-52⟩. ⟨inserm-00626327⟩
576 View
246 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More