The atypical protein kinase C isoform, zPKC, has been implicated in the control of extracellular signalregulated kinase (ERK) and nuclear factor (NF)-kB pathways. Recent evidence from zPKC knock-out mice demonstrates that this kinase is important for NF-kB transcriptional activity but not for ERK activation in embryonic ®broblasts. The lack of zPKC produces in mice a number of alterations in the development of secondary lymphoid tissues that could be accounted for, at least in part, by defects in B-cell function. Here, we present evidence that the loss of zPKC selectively impairs signaling through the B-cell receptor, resulting in inhibition of cell proliferation and survival, as well as defects in the activation of ERK and the transcription of NF-kB-dependent genes. Furthermore, zPKC±/± mice are unable to mount an optimal T-cell-dependent immune response. Collectively, these results genetically establish a critical role for zPKC in B-cell function in vitro and in vivo.

The formation or suppression of particular structures is a major change occurring in development and evolution. One example of such change is the absence of the seventh abdominal segment (A7) in Drosophila males. We show here that there is a down-regulation of EGFR activity and fewer histoblasts in the male A7 in early pupae. If this activity is elevated, cell number increases and a small segment develops in the adult. At later pupal stages, the remaining precursors of the A7 are extruded under the epithelium. This extrusion requires the up-regulation of the HLH protein Extramacrochetae and correlates with high levels of spaghetti-squash, the gene encoding the regulatory light chain of the non-muscle myosin II. The Hox gene Abdominal-B controls both the down-regulation of spitz, a ligand of the EGFR pathway, and the up-regulation of extramacrochetae, and also regulates the transcription of the sex-determining gene doublesex. The male Doublesex protein, in turn, controls extramacrochetae and spaghetti-squash expression. In females, the EGFR pathway is also down-regulated in the A7 but extramacrochetae and spaghetti-squash are not up-regulated and extrusion of precursor cells is almost absent. Our results show the complex orchestration of cellular and genetic events that lead to this important sexually dimorphic character change.

A central issue of myogenesis is the acquisition of identity by individual muscles. In Drosophila, at the time muscle progenitors are singled out, they already express unique combinations of muscle identity genes. This muscle code results from the integration of positional and temporal signalling inputs. Here we identify, by means of loss-of-function and ectopic expression approaches, the Iroquois Complex homeobox genes araucan and caupolican as novel muscle identity genes that confer lateral transverse muscle identity. The acquisition of this fate requires that Araucan/Caupolican repress other muscle identity genes such as slouch and vestigial. In addition, we show that Caupolican-dependent slouch expression depends on the activation state of the Ras/Mitogen Activated Protein Kinase cascade. This provides a comprehensive insight into the way Iroquois genes integrate in muscle progenitors, signalling inputs that modulate gene expression and protein activity.