Due to the evolutionary conservation of the regulation of hematopoiesis, Drosophila
provides an excellent model organism to study blood cell differentiation and hematopoietic
stem cell (HSC) maintenance. The larvae of Drosophila melanogaster respond to immune
induction with the production of special effector blood cells, the lamellocytes, which
encapsulate and subsequently kill the invader. Lamellocytes differentiate as a result
of a concerted action of all three hematopoietic compartments of the larva: the lymph
gland, the circulating hemocytes, and the sessile tissue. Within the lymph gland,
the communication of the functional zones, the maintenance of HSC fate, and the differentiation
of effector blood cells are regulated by a complex network of signaling pathways.
Applying gene conversion, mutational analysis, and a candidate based genetic interaction
screen, we investigated the role of Headcase (Hdc), the homolog of the tumor suppressor
HECA in the hematopoiesis of Drosophila. We found that naive loss-of-function hdc
mutant larvae produce lamellocytes, showing that Hdc has a repressive role in effector
blood cell differentiation. We demonstrate that hdc genetically interacts with the
Hedgehog and the Decapentaplegic pathways in the hematopoietic niche of the lymph
gland. By adding further details to the model of blood cell fate regulation in the
lymph gland of the larva, our findings contribute to the better understanding of HSC
maintenance.
