Muscle–Tendon Interactions in the Absence of Bones: Lessons from the Fruit Fly, Drosophila - Structural Interfaces and Attachments in Biology - page 115

the development of the MTJs, and the molecular pathways that determine the
structural elements within the fly tendons and provide them with the ability to
resist muscle contractions.
6.2 Early Determination of Tendons Is Independent
of Muscle Cells
The intricate pattern of tendon cells within the ectoderm emerges in parallel to
muscle founder cell determination (Fig. 6.1a ). One of the earliest genes that induce
tendon progenitor cells within the ectoderm is the EGR-like transcription factor,
StripeB, one of the two isoforms produced by the stripe gene [ 5 , 6 ]. The StripeB
transcription factor is less active than the alternate StripeA isoform, whose expres-
sion is activated at a later developmental stage following the interaction of the
tendon with the muscle [ 7 ]. StripeB expression is promoted by signaling pathways
involved in the patterning of the embryonic ectoderm including Wg- Hh- Notch-
and EGFR pathways [ 8 ]. Direct Stripe induction is provided by the Wg and Hh
signaling pathways, as both TCF and Ci binding sites were shown to be functional
in the stripe promoter region [ 9 ]. StripeB overexpression promotes the beta-gal
expression of an enhancer trap inserted in the stripe promoter region [ 10 ],
demonstrating that StripeB positively regulates its own transcription. Once
activated, at stage 11-12 of embryonic development, the ectodermal cells are
transformed into tendon progenitor cells capable of directing the correct targeting
of the muscle cells that migrate towards the Stripe-positive tendon cells (Fig. 6.1b ).
Stripe also mediates the induction of adult tendon cells in the fly's thorax [ 11 ].
Interestingly, Stripe expression in the thorax antagonizes the expression of AC-S
proneural genes, inhibiting sensory organ precursor formation in the areas of future
muscle attachment sites. Thus, Stripe expression divides the future adult fly thorax
into a Stripe-positive domain, in which tendon cells develop, and a Stripe-negative
domain, where sensory bristles form. This mutual exclusion between tendons and
neural tissue is conserved in evolution [ 12 ].
Several genes involved in muscle targeting to tendon cells are positively
regulated by Stripe activity in the embryo, including slit , tsp , lrt, and slow
[ 13 - 17 ]. Interestingly, although Stripe is sufficient to induce their expression,
some of these genes are detected at low expression levels even in stripe mutant
embryos, raising the possibility that segment polarity genes initially activate a set of
tendon-specific genes including StripeB. StripeB then maintains and amplifies the
expression of these genes as well as its own transcription, transforming these
ectodermal cells into tendon progenitor cells (Fig. 6.2 ). However, the final differ-
entiation of these progenitor cells depends on their specific interaction with
muscles.
Posttranscriptional downregulation of StripeB levels in the tendon progenitor
cells is provided by the long isoform of the RNA-binding protein Held Out Wing