Cell Adhesion-Mediated Actomyosin Assembly Regulates the Activity of Cubitus Interruptus for Hematopoietic Progenitor Maintenance in Drosophila

Abstract

The actomyosin network is involved in crucial cellular processes including morphogenesis, cell adhesion, apoptosis, proliferation, differentiation, and collective cell migration in Drosophila , Caenorhabditis elegans , and mammals. Here, we demonstrate that Drosophila larval blood stem-like progenitors require actomyosin activity for their maintenance. Genetic loss of the actomyosin network from progenitors caused a decline in their number. Likewise, the progenitor population increased upon sustained actomyosin activation via phosphorylation by Rho-associated kinase. We show that actomyosin positively regulates larval blood progenitors by controlling the maintenance factor Cubitus interruptus (Ci). Overexpression of the maintenance signal via a constitutively activated construct (ci.HA) failed to sustain Ci-155 in the absence of actomyosin components like Zipper (zip) and Squash (sqh), thus favoring protein kinase A (PKA)-independent regulation of Ci activity. Furthermore, we demonstrate that a change in cortical actomyosin assembly mediated by DE-cadherin modulates Ci activity, thereby determining progenitor status. Thus, loss of cell adhesion and downstream actomyosin activity results in desensitization of the progenitors to Hh signaling, leading to their differentiation. Our data reveal how cell adhesion and the actomyosin network cooperate to influence patterning, morphogenesis, and maintenance of the hematopoietic stem-like progenitor pool in the developing Drosophila hematopoietic organ.

Single-cell transcriptome maps of myeloid blood cell lineages in Drosophila

“…First, prohemocytes differ in the expression of cell cycle regulators, implying an asynchrony of prohemocyte development and their states. This observation also accounts for the stochastic cell cycle patterns visualized with the UAS-FUCCI system 46 . Second, we observed dynamic expression patterns of development-related or DNA replication-related and proliferation-related genes in early or late prohemocytes, respectively.…”

“…Prohemocytes have been widely considered to represent a uniform cell population based on the expression of marker genes, domeless or Tep4. However, recent studies have suggested their heterogeneity based on uneven expressions of cell cycle markers or bifurcated col expressions 46,47 . In support of these studies, our unbiased subclustering of primary clusters identified different statuses of prohemocytes.…”

Intermediate Progenitor cells provide a transition between hematopoietic progenitors and their differentiated descendants

“…The MZ cells are also fairly quiescent (Jung et al, 2005;Krzemien et al, 2010;Lebestky et al, 2003), but they are largely held in G2 (Sharma et al, 2019) Girard et al, 2020). We should note that the data presented in this study do not preclude the possibility that a few of the hemocytes might form by a parallel mechanism that does not involve the IPs.…”

Lar maintains the homeostasis of the hematopoietic organ in Drosophila by regulating insulin signaling in the niche

“…The lymph gland consists of a cellular niche, the posterior signaling center (PSC), lying adjacent to the medullary zone (MZ), which houses the progenitor cells. Differentiated cells arising from the progenitors populate the peripheral cortical cone (CZ) (Jung et al, 2005;Krzemieńet al, 2007;Mandal et al, 2007;Banerjee et al, 2019;Sharma et al, 2019). Along with its role in progenitor maintenance, the niche is also implicated in mounting an immune response during wasp infection (Sinenko et al, 2011;Louradour et al, 2017;Crozatier et al, 2004).…”

“…It has been well established that the PSC, or niche, in addition to its role in the maintenance of progenitor cells through Hh signaling (Mandal et al, 2007;Sharma et al, 2019;Tokusumi et al, 2010;Baldeosingh et al, 2018;Banerjee et al, 2019), evokes PVF-PVR signaling in the CZ. This signaling impinges on MZ cells and brings quiescence to the otherwise proliferating progenitors (Mondal et al, 2011).…”