MESODERMAL CELL FATE DECISIONS IN DROSOPHILA ARE UNDER THE CONTROL OFTHE LINEAGE GENES NUMB, NOTCH, AND SANPODO

In Drosophila, much has been learned about the specification of neuron al cell fates but little is known about the lineage of mesodermal cell s with different developmental fates. Initially in development, indivi dual mesodermal precursor cells are singled out to become the founder cells for specific muscles. The selection of muscle founder cells is t hought to employ a Notch-mediated process of lateral inhibition, simil ar to what is observed for the specification of neural precursors. The se muscle founder cells then seem to fuse with the surrounding, uncomm itted myocytes inducing the formation of muscle fiber syncytia. In con trast, the differentiated progeny of neural precursor cells are usuall y the result of a fixed pattern of asymmetric cell divisions which are directed. in part, by interactions between Numb, a localized intracel lular-receptor protein, Sanpodo (Spdo), a potential tropomodulin homol og, and Notch, a transmembrane receptor protein. Here, we have investi gated the role of these neural lineage genes in the cell fate specific ation of muscle and heart precursors. In particular, we have focused o n a progenitor cell that is likely to produce a mixed lineage, generat ing both a pericardial heart cell and a somatic muscle founder cell. W e show th;lt the asymmetric segregation of Numb into one of these daug hter cells antagonizes the function of Notch and spdo by preventing th e presumptive muscle founder from assuming the same fate as its cardia c sibling. Our results suggest that asymmetric cell divisions, in addi tion to the previously-documented inductive mechanisms, play a major r ole in cardiac and somatic muscle patterning and that additionally the cytoskeleton may have a role in the asymmetrical localization of cell fate determinants. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.