Hematopoietic progenitor choice between multipotency and differentiation is tightly
regulated by intrinsic factors and extrinsic signals from the surrounding microenvironment.
The Drosophila melanogaster hematopoietic lymph gland has emerged as a powerful tool
to investigate mechanisms that regulate hematopoietic progenitor choice in vivo. The
lymph gland contains progenitor cells, which share key characteristics with mammalian
hematopoietic progenitors such as quiescence, multipotency and niche dependence. The
lymph gland is zonally arranged, with progenitors located in medullary zone, differentiating
cells in the cortical zone, and the stem cell niche or Posterior Signaling Center
(PSC) residing at the base of the medullary zone (MZ). This arrangement facilitates
investigations into how signaling from the microenvironment controls progenitor choice.
The Drosophila Friend of GATA transcriptional regulator, U-shaped, is a conserved
hematopoietic regulator. To identify additional novel intrinsic and extrinsic regulators
that interface with U-shaped to control hematopoiesis, we conducted an in vivo screen
for factors that genetically interact with u-shaped. Smoothened, a downstream effector
of Hedgehog signaling, was one of the factors identified in the screen. Here we report
our studies that characterized the relationship between Smoothened and U-shaped. We
showed that the PSC and Hedgehog signaling are required for U-shaped expression and
that U-shaped is an important intrinsic progenitor regulator. These observations identify
a potential link between the progenitor regulatory machinery and extrinsic signals
from the PSC. Furthermore, we showed that both Hedgehog signaling and the PSC are
required to maintain a subpopulation of progenitors. This led to a delineation of
PSC-dependent versus PSC-independent progenitors and provided further evidence that
the MZ progenitor population is heterogeneous. Overall, we have identified a connection
between a conserved hematopoietic master regulator and a putative stem cell niche,
which adds to our understanding of how signals from the microenvironment regulate
progenitor multipotency.
