Migration of the tracheal cells relies on cues provided by nearby cells; however little is known about how these signals specify a migratory path. of a cell surface molecule with expression restricted to a subset of tracheal cells that all migrate in a given direction. We have also found that expression of PS1 in the visceral branch is usually regulated by the genes that direct tracheal cell migration showing that integrin expression is usually part of the cell-fate program that they specify. These results support a model in which signal transduction determines the tracheal NVP-BSK805 migratory pathways by regulating the expression of cell surface proteins which in turn interact with surface molecules on the surrounding cell population. is usually a NVP-BSK805 particularly tractable model for the study of cell migration and in particular of the mechanisms that guideline cells to migrate in specific directions (for review see Hogan and Yingling 1998; Metzger and Krasnow 1999). The larval tracheal system of is usually a complex tubular network that conducts oxygen from the exterior to the internal tissues. It arises from the tracheal placodes clusters of ectodermal cells that appear at each side of 10 embryonic segments from the second thoracic segment to the eighth abdominal segment. The cells of each cluster invaginate and migrate in different and stereotyped directions to form each of the primary tracheal branches (Manning and Krasnow 1993). The general conclusion from many studies is that NVP-BSK805 the direction of migration of the tracheal cells relies on a set of positional cues provided by nearby cells. On the one hand (expression in small clusters of epidermal cells the outgrowth of the visceral branch is usually directed toward clusters of position-specific (PS) integrins are most NVP-BSK805 similar to the β1 family of vertebrate integrins and one βPS subunit is likely to form heterodimers with all five of the αPS subunits encoded by the genome (Brown et al. 2000). As with the majority of integrins the PS integrins are thought to function by binding ligands within the extracellular matrix. To NVP-BSK805 see whether integrins might be playing a role in tracheal migration we examined their expression in the tracheal cells. We have found that around stage 11 the αPS1 mRNA is usually specifically expressed in those tracheal cells that give rise to the visceral branch although we also detect weak expression in the dorsal cells (Fig. ?(Fig.2B-D).2B-D). Localized expression in the visceral branch is usually more clearly evident at stage 12 during germ-band retraction when the main branches appear as protrusions (Fig ?(Fig2A E-G).2A E-G). αPS1 mRNA expression is usually maintained during stage 13 as the visceral branch grows and is lost by stage 14 (Fig. ?(Fig.2H-J).2H-J). We have also analyzed whether there is expression of the αPS2 subunit in the tracheal cells and did not detect expression (data not shown). Physique 2 Expression of αPS1 in the visceral branches. ((mutant embryos the visceral branches fail to develop properly (Fig. ?(Fig.3D).3D). We observe that although the visceral branches migrate normally toward the gut and reach and contact the visceral mesoderm (Fig. ?(Fig.3E) 3 they Fndc4 do not migrate normally along the visceral mesoderm (Figs. ?(Figs.3F3F and ?and4A).4A). At a stage when the cells of the visceral branches have migrated along the visceral mesoderm in wild-type embryos in mutant embryos the NVP-BSK805 visceral branches cells remain at their initial point of contact with the visceral mesoderm (Fig. ?(Fig.3F).3F). Some delayed migration can also be observed at later stages. Other aspects of visceral branch development are not affected in mutant embryos; for instance the mispositioned visceral branches form fine branches later in development (Fig. ?(Fig.3D).3D). Physique 3 Migration of the visceral branches is usually impaired in integrin mutants. We examined the tracheal mutant phenotypes by using either the mAb2A12 antibody which recognizes the tracheal lumen in stage 15 embryos (… Physique 4 Tissue-specific requirement of αPS1 and αPS2. Dorsal view of tracheae at stage 14 embryos visualized by the mAb2A12 antibody. ((mutant embryos visceral branch formation is also impaired (Fig. ?(Fig.3G).3G). As is the case for mutant embryos the visceral branches of mutant embryos reach the visceral mesoderm but fail to migrate over it (Figs. ?(Figs.3H-I3H-I and 4D). However the defects are usually milder than in mutant embryos. We also observe that later branching is not affected (Fig. ?(Fig.3G).3G). The defect in visceral branch formation in mutant embryos is not due to a failure of expression as it appears at the right.