Cell-Cell Interaction During Drosophila Embryogenesis
75
in lateral tracheal cells respecifies their anteroposterior migration to a
dorsoventral migration behavior (Chen et al. 1998).
5.2.5 Guiding Migration of Tracheal Cells: A Working Model
The genetic and molecular studies of embryonic tracheal development
have provided a relatively detailed picture of how the major tracheal
branches are established after the invagination of the tracheal placode.
Clearly, one of the major determinants of the primary branching pattern
is the FGF ligand encoded by the bnl gene. The dynamic spatial expression of BNL in ectodermal and mesodermal cells around the tracheal sac
prefigures the direction of migration of tracheal cells. Gain-of-function
experiments are entirely consistent with a chemoattractive function of
BNL. But how does the spatial activation of the BNL receptor BTL, a
transmembrane receptor tyrosine kinase, lead to the directed outgrowth
of tracheal cells? One important novel and essential component of BTL(and HTL-)mediated migration is encoded by the do! gene. DOF links
the activated receptor to the RAS-MAPK cascade but it is unlikely that
this represents the only function of DOF. DOF might also act as a
mediator between the activated receptor and cytoskeletal components,
ultimately leading to a polarization of the responding cells. Based on
experiments with activated hybrid receptors, it has indeed been argued
that the activation of the RAS-MAPK cascade is not sufficient for
directed tracheal migration (Lee et al. 1997). It is likely that local BTL
signaling polarizes the responding cells, leading to the local activation
of a cellular locomotion "machinery" (Mitchison and Cramer 1996;
Lauffenburger and Horvitz 1996). The isolation and characterization of
DOF provides a promising entry point to study how the FGFRs BTL and
BNL affect cellular migration behaviors. At present, we are trying to
isolate proteins that interact with DOF in an attempt to link receptor
activation to directed migration.
Although it remains to be shown whether FGFR signaling to the
nucleus is important for directed migration, it is clear that DPP signaling
in dorsal and ventral cells is essential for their directed migration and is
mediated via the transcriptional induction of two genes which in tum
encode transcription factors (KNIRPS and KNIRPS RELATED; Chen
et al. 1998). Dorsal and ventral tracheal cells have to receive and re-
75
in lateral tracheal cells respecifies their anteroposterior migration to a
dorsoventral migration behavior (Chen et al. 1998).
5.2.5 Guiding Migration of Tracheal Cells: A Working Model
The genetic and molecular studies of embryonic tracheal development
have provided a relatively detailed picture of how the major tracheal
branches are established after the invagination of the tracheal placode.
Clearly, one of the major determinants of the primary branching pattern
is the FGF ligand encoded by the bnl gene. The dynamic spatial expression of BNL in ectodermal and mesodermal cells around the tracheal sac
prefigures the direction of migration of tracheal cells. Gain-of-function
experiments are entirely consistent with a chemoattractive function of
BNL. But how does the spatial activation of the BNL receptor BTL, a
transmembrane receptor tyrosine kinase, lead to the directed outgrowth
of tracheal cells? One important novel and essential component of BTL(and HTL-)mediated migration is encoded by the do! gene. DOF links
the activated receptor to the RAS-MAPK cascade but it is unlikely that
this represents the only function of DOF. DOF might also act as a
mediator between the activated receptor and cytoskeletal components,
ultimately leading to a polarization of the responding cells. Based on
experiments with activated hybrid receptors, it has indeed been argued
that the activation of the RAS-MAPK cascade is not sufficient for
directed tracheal migration (Lee et al. 1997). It is likely that local BTL
signaling polarizes the responding cells, leading to the local activation
of a cellular locomotion "machinery" (Mitchison and Cramer 1996;
Lauffenburger and Horvitz 1996). The isolation and characterization of
DOF provides a promising entry point to study how the FGFRs BTL and
BNL affect cellular migration behaviors. At present, we are trying to
isolate proteins that interact with DOF in an attempt to link receptor
activation to directed migration.
Although it remains to be shown whether FGFR signaling to the
nucleus is important for directed migration, it is clear that DPP signaling
in dorsal and ventral cells is essential for their directed migration and is
mediated via the transcriptional induction of two genes which in tum
encode transcription factors (KNIRPS and KNIRPS RELATED; Chen
et al. 1998). Dorsal and ventral tracheal cells have to receive and re-