In a paper published online in advance in Nature this week, MIT's Tyler Jacks and his colleagues describe the "suppression of lung adenocarcinoma progression by Nkx2-1," the NK2-related homeobox transcription factor. In a KrasLSL-G12D/+;p53flox/flox mouse model, the team found that "Nkx2-1 negativity is pathognomonic of high-grade poorly differentiated tumors." In their subsequent gain- and loss-of-function manipulations, the researchers found that the transcription factor controls tumor differentiation but also limits its metastatic potential. "Thus, the oncogenic and suppressive functions of Nkx2-1 in the same tumor type substantiate its role as a dual function lineage factor," Jacks et al. write.
In another Nature online advance publication, an international team led by investigators at Johns Hopkins University shows that mitotic progenitor cells' switch from proliferation to migration in the developing cortex is dependent upon a molecular switch at DISC1, which is a known "major susceptibility factor for several mental disorders." By charting the signaling pathway through which DISC1 switches from "maintaining proliferation of mitotic progenitor cells to activating migration of postmitotic neurons in mice," the team identified phosphyorylation of this protein at serine 710 "as a key developmental switch."
Over in Nature Genetics, members of the Alzheimer's Disease Genetics Consortium report results of their genome-wide association study, which consisted of a discovery stage and two replication stages. The researchers found that common variants at MS4A4/MS4A6E, CD2AP, CD33, and EPHA1 are significantly associated with late-onset Alzheimer's disease susceptibility.
In a companion paper, an international team led by investigators at Cardiff University test the susceptibility loci being reported by the Alzheimer's Disease Genetics Consortium using four genome-wide association data sets. In its meta-analysis, the team found evidence to suggest that ABCA7 and the MS4A gene cluster are also significant late-onset Alzheimer's disease susceptibility loci. "We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP, CD33, and EPHA1," the team writes.