ETS‐family genes in pancreatic development

Abstract

ETS-family factors play major roles in development and cancer, notably as critical targets for extra-cellular signaling pathways, including MAPK-signaling. Given the presently limited knowledge on the role of ETS-factors in pancreatic development, we here sought to characterize all 26 individual members of the ETS-family in relation to pancreatic development using a combination of genomics, RT-PCR, and histological techniques. This analysis uncovers 22 ETS family genes displaying select spatial and temporal expression patterns in the developing pancreas. Highly specific expression of ETS-family components is observed in pancreatic progenitor cells or the associated embryonic mesenchyme. Other members are linked to the differentiation of more mature pancreatic cells, including exocrine and endocrine cell types. We find that two members of the Etv subfamily, Etv4 and Etv5, are expressed in cells proximal to pancreatic mesenchyme, and, furthermore, induced in FGF10-arrested pancreatic progenitors suggesting that these factors mediate mesenchymal-to-epithelial signaling. Developmental Dynamics 236:3100 -3110, 2007.

Loss of Extracellular Superoxide Dismutase Leads to Acute Lung Damage in the Presence of Ambient Air

“…The large accumulation of granulocytes occurs in numerous types in acute lung injury. 43,44 As seen in Figure 4, tamoxifen injection caused a small increase in granulocytes in wild-type mice. We considered the possibility that tamoxifen could induce an inflammatory response in the absence of SOD3 and that the acute reduction in SOD3 caused by tamoxifen was not the cause of lung damage and death.…”

“…50 The transcription factor early growth response (Erg-1) has been shown to be involved in the tissue factor gene regulation, 51 and Etv5 is a member of the Ets transcription factor family. 44 Other cell signaling genes that are highly expressed in the SOD3 Ϫ/Ϫ lungs include the FGF receptor 3, which has been implicated in lymphatic vessel development 52 ; the Ras effector family member Rassf3, which can function as a tumor suppressor 53 ; and ARf3, a member of the small G-protein family that is involved in epithelial cell proliferation. 54 The extracellular matrix encoding mRNAs, utrophin, and Ndst were also increased in the SOD3 Ϫ/Ϫ mice compared to the other animals.…”

The nuclear hormone receptor family member NR5A2 controls aspects of multipotent progenitor cell formation and acinar differentiation during pancreatic organogenesis

“…The mRNA for DUSP9, a paralog of the dual-function phosphatase DUSP6, which controls the persistence of the activated RET, decreased 2.5-fold. ETV4 and ETV5, which mediate RETactivated transcriptional control, are prominent in developing pancreas at this stage and are restricted to the branching epithelial tips (Kobberup et al, 2007), but their mRNA levels are unaffected in the Nr5a2 mutant. NR5A2 is bound to pancreatic transcriptional control regions of each of these genes, based on co-localization with the PTF1-L complex and markers of active enhancers (supplementary material Fig.…”

The Ets Transcription Factor EHF as a Regulator of Cornea Epithelial Cell Identity

“…Previous studies found that EHF expression is enriched in epithelial tissues (95), particularly glandular epithelia, where it binds targets related to late stage differentiation (96). It has been shown to be highly expressed in cornea (97), conjunctiva (53), and prostate endocrine cells (98), although the roles of EHF in these tissues are yet to be described.…”