Matrix glycoprotein Papilin maintains the haematopoietic progenitor pool in the Drosophila lymph glands.

Differentiation of prohaemocytes, the precursors of Drosophila blood cells (haemocytes), and the release of haemocytes from the lymph gland, a major larval haematopoietic organ, are vital responses to wasp infestation or tissue degeneration. While cells and extracellular matrices (ECMs) in the lymph gland play a crucial role in haemocyte differentiation, the underlying mechanisms remain unclear. Here, we show that the matrix glycoprotein Papilin (Ppn) is essential for maintaining the prohaemocyte population in lymph glands. In Ppn-depleted larvae, haemocyte differentiation increased with a reduction in the prohaemocyte-containing medullary zone, and lymph gland lobes dispersed prematurely. Ppn was synthesised by plasmatocytes, forming lamellae mainly in the medullary zone. Microbial infection or wasp infestation disrupted the Ppn meshwork within lymph glands. Ppn colocalised with collagen, laminin, nidogen, and perlecan. Ppn depletion disrupted the ECM structure, including perlecan organisation. Phenotypes caused by Ppn depletion were partially rescued by perlecan overexpression or inactivation of the epidermal growth factor receptor (EGFR) pathway. Thus, Ppn is critical in maintaining lymph gland architecture and regulating haemocyte differentiation, highlighting an intricate interaction between ECMs and signalling pathways in haematopoiesis.