Monocytes block tumor access to the lung: Metastatic cancer is especially hard to treat. In order to find potential new therapeutic targets, scientists are trying to understand the cellular events that promote or prevent metastasis. Hanna et al. now report a role for patrolling monocytes in blocking tumor metastasis to the lungs in mice. Tumors in mice engineered to lack patrolling monocytes showed increased metastasis to the lung but not to other tissues. Patrolling monocytes resided in the microvasculature of the lung, where they engulfed tumor material, which may explain how these cells prevent tumors from colonizing the lung. Science , this issue p. 985

We previously identified a stromal cell-derived inducing activity (SDIA), which induces differentiation of neural cells, including midbrain tyrosine hydroxylase-positive (TH ⁺ ) dopaminergic neurons, from mouse embryonic stem cells. We report here that SDIA induces efficient neural differentiation also in primate embryonic stem cells. Induced neurons contain TH ⁺ neurons at a frequency of 35% and produce a significant amount of dopamine. Interestingly, differentiation of TH ⁺ neurons from undifferentiated embryonic cells occurs much faster in vitro (10 days) than it does in the embryo (≈5 weeks). In addition, 8% of the colonies contain large patches of Pax6 ⁺ -pigmented epithelium of the retina. The SDIA method provides an unlimited source of primate cells for the study of pathogenesis, drug development, and transplantation in degenerative diseases such as Parkinson's disease and retinitis pigmentosa.

Transcription factors involved in the specification and differentiation of neurons often continue to be expressed in the adult brain, but remarkably little is known about their late functions. Nurr1, one such transcription factor, is essential for early differentiation of midbrain dopamine (mDA) neurons but continues to be expressed into adulthood. In Parkinson's disease, Nurr1 expression is diminished and mutations in theNurr1gene have been identified in rare cases of disease; however, the significance of these observations remains unclear. Here, a mouse strain for conditional targeting of theNurr1gene was generated, andNurr1was ablated either at late stages of mDA neuron development by crossing with mice carrying Cre under control of the dopamine transporter locus or in the adult brain by transduction of adeno-associated virus Cre-encoding vectors.Nurr1deficiency in maturing mDA neurons resulted in rapid loss of striatal DA, loss of mDA neuron markers, and neuron degeneration. In contrast, a more slowly progressing loss of striatal DA and mDA neuron markers was observed after ablation in the adult brain. As in Parkinson's disease, neurons of the substantia nigra compacta were more vulnerable than cells in the ventral tegmental area whenNurr1was ablated at late embryogenesis. The results show that developmental pathways play key roles for the maintenance of terminally differentiated neurons and suggest that disrupted function of Nurr1 and other developmental transcription factors may contribute to neurodegenerative disease.