An essential function of the mitogen‐activated protein kinase Erk2 in mouse trophoblast development

Abstract

The closely related mitogen-activated protein kinase isoforms extracellular signal-regulated kinase 1 (ERK1) and ERK2 have been implicated in the control of cell proliferation, differentiation and survival. However, the specific in vivo functions of the two ERK isoforms remain to be analysed. Here, we show that disruption of the Erk2 locus leads to embryonic lethality early in mouse development after the implantation stage. Erk2 mutant embryos fail to form the ectoplacental cone and extra-embryonic ectoderm, which give rise to mature trophoblast derivatives in the fetus. Analysis of chimeric embryos showed that Erk2 functions in a cell-autonomous manner during the development of extra-embryonic cell lineages. We also found that both Erk2 and Erk1 are widely expressed throughout early-stage embryos. The inability of Erk1 to compensate for Erk2 function suggests a specific function for Erk2 in normal trophoblast development in the mouse, probably in regulating the proliferation of polar trophectoderm cells.

MAPK signaling in inflammation-associated cancer development

“…Other studies also show that ERK1-null mice have increased locomotor activity (Mazzucchelli et al, 2002) and impaired adipocyte differentiation (Bost et al, 2005). In contrast, ERK2-null mice show completely different phenotypes; these mice die at embryonic day 6.5-8.5 due to impaired mesoderm differentiation and placental development (Hatano et al, 2003;Saba-El-Leil et al, 2003;Yao et al, 2003).…”

Dopamine D1 vs D5 receptor-dependent induction of seizures in relation to DARPP-32, ERK1/2 and GluR1-AMPA signalling

“…Given that ERK1/2 activation has recently been observed in response to seizure-producing stimuli at nondopamine receptors (Merlo et al, 2004), it is plausible that ERK1/2 function as coincident detectors of generalised epileptiform activity. Although targeted deletion of the ERK2 gene is lethal in utero (Yao et al, 2003;Saba-El-Leil et al, 2003), future studies examining the seizure profile of diverse chemoconvulsants, including SKF 83822, in ERK1 knockouts (Pages et al, 1999) or in combination with SL327 (an upstream inhibitor of ERK) may reveal novel strategies for seizure prevention. Given the present effects of SKF 83822 on the phosphorylation of DARPP-32, ERK1/2 and GluR1-AMPA receptor subunits in wild-type mice, a priority for future experiments will be to test the hypothesis that phosphorylation of these proteins is reduced in D 1 /D 5 receptor and DARPP-32 knockouts receiving a convulsant dose of SKF 83822.…”

Conferring specificity on the ubiquitous Raf/MEK signalling pathway

“…In a similar vein, the ablation of ERK-1 does not compromise viability and causes rather subtle changes in the functions of T-cells and memory. In contrast, knocking out ERK-2 is embryonic lethal (Saba-El-Leil et al, 2003). At present, the Figure 1 PC12 cell model of neuronal differentiation.…”