Macrophages have a critical role in inflammatory and immune responses through their ability to recognize and engulf apoptotic cells 1 . Here we show that macrophages initiate a cell-death programme in target cells by activating the canonical WNT pathway. We show in mice that macrophage WNT7b is a short-range paracrine signal required for WNT-pathway responses and programmed cell death in the vascular endothelial cells of the temporary hyaloid vessels of the developing eye. These findings indicate that macrophages can use WNT ligands to influence cellfate decisions-including cell death-in adjacent cells, and raise the possibility that they do so in many different cellular contexts.In most systems, it has largely been assumed that macrophage involvement in programmed cell death comes after the apoptotic event, and is a response to the presence of membranetethered or soluble 'eat-me' signals from dead and dying cells. However, in some circumstances phagocytes actively induce programmed cell death. In mice, macrophages are required for the programmed regression of temporary capillary networks within the

Neurobiology of speech and language has previously been studied in the KE family, in which half of the members have severe impairment in both speech and language. The gene responsible for the phenotype was mapped to chromosome 7q31 and identified as the FOXP2 gene, coding for a transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain. Because of linkage studies implicating 7q31 in autism, where language impairment is a component of the disorder, and in specific language impairment, FOXP2 has also been considered as a potential susceptibility locus for the language deficits in autism and͞or specific language impairment. In this study, we characterized mice with a disruption in the murine

Epithelial gene expression in the lung is thought to be regulated by the coordinate activity of several different families of transcription factors including the Fox family of winged-helix/forkhead DNA-binding proteins. In this report, we have identified and characterized two members of this Fox gene family, Foxp1 and Foxp2, and show that they comprise a new subfamily of Fox genes expressed in the lung. Foxp1 and Foxp2 are expressed at high levels in the lung as early as E12.5 of mouse development with Foxp2 expression restricted to the airway epithelium. In addition, Foxp1 and Foxp2 are expressed at lower levels in neural, intestinal, and cardiovascular tissues during development. Upon differentiation of the airway epithelium along the proximal-distal axis, Foxp2 expression becomes restricted to the distal alveolar epithelium whereas Foxp1 expression is observed in the distal epithelium and mesenchyme. Foxp1 and Foxp2 can regulate epithelial lung gene transcription as was demonstrated by their ability to dramatically repress the mouse CC10 promoter and, to a lesser extent, the human surfactant protein C promoter. In addition, GAL4 fusion proteins encoding subdomains of Foxp1 and Foxp2 demonstrate that an independent and homologous transcriptional repression domain lies within the N-terminal end of the proteins. Together, these studies suggest that Foxp1 and Foxp2 are important regulators of lung epithelial gene transcription.The mouse lung arises from the laryngo-tracheal groove in the primitive foregut at approximately gestational day 9.5 (E9.5) of mouse development (for review see Refs. 1 and 2). Further development through a process termed branching morphogenesis results in a primitive epithelial lined tubular structure by E12.5. Additional differentiation of this primitive epithelial lining along the proximal-distal axis during the pseudoglandular stage of development results in highly differentiated airway epithelial cells capable of surfactant protein expression and gas exchange essential for postnatal lung function. The molecular mechanisms regulating the process of branching morphogenesis and proximal-distal patterning of the lung epithelium are poorly understood. However, recent reports have indicated that lung-specific gene expression is regulated at the level of transcription (reviewed in Refs. 1 and 2). Several transcription factors have been implicated in this transcriptional program including the homeodomain protein Nkx2.1/TTF-1, the zinc-finger transcription factor GATA-6, and members of the winged-helix/forkhead (Fox) family of transcription factors (3-10).The Fox family of transcription factors is a large group of proteins that share a common DNA binding domain termed a winged-helix or forkhead domain after the founding member of this group, the forkhead gene in Drosophila (for review see Ref. 11). Several Fox genes are expressed in the lung and have been implicated as important regulators of lung gene transcription including Foxa1, Foxa2, Foxf1, Foxf2, and Foxj1. These Fox family members are ...