Cooperative Mesp activity is required for normal somitogenesis along the anterior-posterior axis.

Mesp2 is a bHLH-type transcription factor that plays a key role during somitogenesis. Mesp2 is transiently expressed and is quickly degraded once translated. In our current study, we find that Mesp2 contains a degradation domain, which acts as a target of proteasome-mediated proteolysis and appears to play this role in vivo. We have also defined the nuclear localization signals (NLS) and constructed a minimum Mesp2 protein (P2-HD) composed of the NLS, bHLH and the degradation domains. The ability of the P2-HD as a transcription factor in vivo was examined. Some of the defects that had been previously observed in the Mesp2-null mice were rescued in the knock-in mice but only in the posterior half of the body, indicating differential effects of P2-HD along the anterior-posterior (AP) axis. In addition, quantitative analysis of the expression along the AP axis revealed that the relative levels of Mesp2 increased, whereas Mesp1 is down-regulated in the later stages of development by the activities of Mesp2 in the wild-type embryo. Moreover, we have found that somitogenesis in the early stages is more susceptible to changes in the Mesp gene dosage, indicating that a threshold level of Mesp activity must be required for the progression of normal somitogenesis.