Ubx-Collier Signaling Cascade Maintains Blood Progenitors In The Posterior Lobes Of The Drosophila Larval Lymph Gland

Drosophila larval hematopoiesis occurs in a specialized multi-lobed organ called the lymph gland. Extensive characterization of the organ has provided mechanistic insights into events related to developmental hematopoiesis. Spanning from the thoracic to the abdominal segment of the larvae, this organ comprises a pair of primary, secondary, and tertiary lobes. Much of our understanding arises from the studies on the primary lobe, while the secondary and tertiary lobes have remained mostly unexplored. Previous studies have inferred that these lobes are composed of progenitors that differentiate during pupation; however, the mechanistic basis of this extended progenitor state remains unclear. This study shows that posterior lobe progenitors are maintained by a local signaling center defined by Ubx and Collier in the tertiary lobe. This Ubx zone in the tertiary lobe shares several markers with the niche of the primary lobe. Ubx domain regulates the homeostasis of the posterior lobe progenitors in normal development and an immune-challenged scenario. Our study establishes the lymph gland as a model to tease out how the progenitors interface with the dual niches within an organ during development and disorders.Author summary Stem and progenitor cells require a niche for their maintenance. Invertebrate models have played a pivotal role in deciphering the signals/crosstalks between stem cell compartments and their niches. The multilobed larval hematopoietic organ or the lymph gland of Drosophila has been extensively used to gain insights into the mechanistic basis of these interactions. The lymph gland consists of cellularly diverse primary lobes, followed by pairs of secondary and tertiary lobes, collectively called posterior lobes. These less explored posterior lobes that houses blood progenitors is the current focus of the study. Based on molecular markers, we propose that the posterior lobes comprise blood cells in a pre-progenitor-like state and an anterior domain in the tertiary lobe that expresses Hox gene Ultrabithorax (Ubx) and high EBF factor Collier/Knot. Employing loss of function, genetic knockdown and overexpression analysis, we demonstrate that the Ubx domain maintains the posterior lobe progenitors' state and fate. Hox gene Antennapedia is known to specify the niche of the primary lobe. Our results elucidate a similar Hox-dependent signaling center essential for maintaining the posterior lobes' blood progenitors. This study raises the possibility of using the lymph gland to explore how multiple niches interact with progenitors during development and disorders.