Yorkie and Scalloped Signaling Regulates Notch-Dependent Lineage Specification during Drosophila Hematopoiesis

Abstract

Summary Cellular microenvironments established by the spatial and temporal expression of specific signaling molecules are critical for both the maintenance and lineage-specific differentiation of progenitor cells. In Drosophila, a population of hematopoietic progenitors, or prohemocytes, within the larval lymph gland [1] gives rise to three mature cell types: plasmatocytes, lamellocytes, and crystal cells. Removal of the secreted signaling molecules Hedgehog [2] and PVF1 [3] from the Posterior Signaling Center (PSC)[2, 4, 5] which acts as a niche, leads to a loss of progenitors and complete differentiation of the lymph gland. Here, we characterize a novel population of signaling cells within the lymph gland, distinct from the PSC, that are required for lineage specific differentiation of crystal cells. We provide evidence that Yorkie[6] and Scalloped[7], the Drosophila homologues of YAP and TEAD, are required in Lineage Specifying Cells to regulate expression of Serrate, the Notch ligand responsible for the initiation of the crystal cell differentiation program[8] [5]. Genetic manipulation of yorkie and scalloped in the lymph gland specifically alters Serrate expression and crystal cell differentiation. Furthermore, Serrate expression in Lineage Specifying Cells is eliminated in the Lymph Gland upon the immune response induced by wasp parasitization to ensure the proper differentiation of lamellocytes at the expense of crystal cells. These findings expand the roles for Yorkie/Scalloped beyond growth to encompass specific cell fate determination in the context of blood development. Similar regulatory functions may extend to their homologues in vertebrate progenitor cell niches that are required for specifying cell fate.

Dpp dependent Hematopoietic stem cells give rise to Hh dependent blood progenitors in larval lymph gland of Drosophila

“…Rather only the crystal cells were labeled by both GFP and RFP (also seen by Hnt). This crystal cell specific restriction of GFP and RFP expression can be explained by requirement of Notch for maturation, maintenance and survival of this cell type (Lebestky et al, 2003; Mukherjee et al, 2011; Terriente-Felix et al, 2013; Duvic et al, 2002; Ferguson and Martinez-Agosto, 2014). …”

A Novel Notch–YAP Circuit Drives Stemness and Tumorigenesis in Embryonal Rhabdomyosarcoma

“…This cross-talk is strikingly cell-type and context specific, because even within one organism (e.g. Drosophila melanogaster ), Notch activates YAP in the lymph gland, inhibits Hippo signaling in the wing disc, and Notch-Hippo have an inverse relationship in oocytes (32–34). Crosstalk between these two pathways in the pediatric cancer eRMS has not yet been studied.…”

Uncoupling of the Hippo and Rho pathways allows megakaryocytes to escape the tetraploid checkpoint

“…Previous reports have demonstrated the importance of the Hippo pathway in fly hematopoiesis. 25,26 It was also reported that key proteins of the Hippo pathway are expressed in mantle cell lymphoma. 27 Furthermore YAP, a key component of the Hippo pathway, is highly expressed in stem cells and decreases progressively during differentiation.…”