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Robo and the Derailed Receptor Tyrosine Kinase pathways [ 13 , 14 , 22 ]. Muscles
express the Robo receptors (Robo and Robo2), and Slit is secreted from tendon cells
as well as from the ventral cord midline. Interestingly, whereas both Slit/Robo and
Derailed pathways repress axon guidance, they appear to mediate attraction of
muscles towards their target tendon cells (an exception is the ventral muscles,
which are repelled from the ventral midline due to Slit activity secreted at the
Recently, an additional novel protein complex expressed by the ventral longitu-
dinal muscles was demonstrated to mediate muscle migration towards tendon cells.
This complex includes the transmembrane protein Kon-Tiki/Perdido, its cytoplas-
mic partner, the PDZ domain protein, Grip, and the cell surface protein, Echinoid
[ 21 , 23 - 25 ]. Kon-Tiki and Grip share a similar phenotype, in which mutant muscles
do not extend towards the tendon cells during their migration, suggesting that they
both mediate a positive attractive cue sensed by the muscle ends. The nature of this
signal has not yet been elucidated.
In summary, the unique bipolar extension of the muscle ends might be dependent
on short-range signals provided by the tendon cells [ 26 ].
6.4 Formation of the Drosophila Myotendinous Junction
In both vertebrates and invertebrates, the correct construction of the MTJ is
essential for force transmission and to counteract muscle contraction by the skeletal
elements via tendon cells. The MTJ consists of hemi-adherens junctions formed
between integrin heterodimers assembled on the muscle and tendon membrane
surfaces together with extracellular matrix (ECM) proteins deposited in between
these cells [ 26 ]. These ECM proteins “glue” both cell types together through
integrin receptors associated with the actin cytoskeleton in the cytoplasm of each
cell. The glue-like ECM material provides elastic properties to the MTJ, and its
unique ultrastructural organization is essential for proper force transmission
(Fig. 6.4 ).
Studies in Drosophila revealed the sequence of events associated with MTJ
formation. Two types of integrin heterodimers mediate MTJ formation, namely
PS on the muscle side [ 27 , 28 ]. They appear
to interact with distinct types of ECM proteins; the tendon-specific
PS on the tendon cell and
interacts with laminin [ 29 , 30 ], whereas the muscle-specific
PS interacts
with Thrombospondin (Tsp) [ 15 , 31 ] and with Tiggrin [ 32 ] (Fig. 6.4 ). Laminin as
well as Tsp are secreted from the tendon cells, and Tiggrin is secreted from the
muscle cell. MTJ dysfunction causes the complete dissociation of muscles from
tendons, leading to embryonic lethality. The most severe muscle detachment
phenotype is obtained in embryos mutant for either
PS or its ECM ligand,
Tsp. Lack of Laminin, and/or
PS leads to a less severe muscle detachment
phenotype, suggesting that the adhesion of the muscle to the tendon-associated
ECM is a critical aspect of the MTJ function.
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