I. Castanon et al., Dimerization partners determine the activity of the Twist bHLH protein during Drosophila mesoderm development, DEVELOPMENT, 128(16), 2001, pp. 3145-3159
The basic helix-loop-helix transcription factor Twist regulates a series of
distinct cell fate decisions within the Drosophila mesodermal lineage. The
se twist functions are reflected in its dynamic pattern of expression, whic
h is characterized by initial uniform expression during mesoderm induction,
followed by modulated expression at high and low levels in each mesodermal
segment, and finally restricted expression in adult muscle progenitors. We
show two distinct partner-dependent functions for Twist that are crucial f
or cell fate choice. We find that Twist can form homodimers and heterodimer
s with the Drosophila E protein homologue, Daughterless, in vitro. Using te
thered dimers to assess directly the function of these two particular dimer
s in vivo, we show that Twist homodimers specify mesoderm and the subsequen
t allocation of mesodermal cells to the somatic muscle fate. Misexpression
of Twist-tethered homodimers in the ectoderm or mesoderm leads to ectopic s
omatic muscle formation overriding other developmental cell fates. In addit
ion, expression of tethered Twist homodimers in embryos null for twist can
rescue mesoderm induction as well as somatic muscle development.
Loss of function analyses, misexpression and dosage experiments, and bioche
mical studies indicate that heterodimers of Twist and Daughterless repress
genes required for somatic myogenesis. We propose that these two opposing r
oles explain how modulated Twist levels promote the allocation of cells to
the somatic muscle fate during the subdivision of the mesoderm. Moreover, t
his work provides a paradigm for understanding how the same protein control
s a sequence of events within a single lineage.