Interdependence of macrophage migration and ventral nerve cord development in Drosophila embryos

Abstract

SUMMARYDuring embryonic development, Drosophila macrophages (haemocytes) undergo a series of stereotypical migrations to disperse throughout the embryo. One major migratory route is along the ventral nerve cord (VNC), where haemocytes are required for the correct development of this tissue. We show, for the first time, that a reciprocal relationship exists between haemocytes and the VNC and that defects in nerve cord development prevent haemocyte migration along this structure. Using live imaging, we demonstrate that the axonal guidance cue Slit and its receptor Robo are both required for haemocyte migration, but signalling is not autonomously required in haemocytes. We show that the failure of haemocyte migration along the VNC in slit mutants is not due to a lack of chemotactic signals within this structure, but rather to a failure in its detachment from the overlying epithelium, creating a physical barrier to haemocyte migration. This block of haemocyte migration in turn disrupts the formation of the dorsoventral channels within the VNC, further highlighting the importance of haemocyte migration for correct neural development. This study illustrates the important role played by the three-dimensional environment in directing cell migration in vivo and reveals an intriguing interplay between the developing nervous system and the blood cells within the fly, demonstrating that their development is both closely coupled and interdependent.

Understanding in vivo blood cell migration—Drosophila hemocytes lead the way

“…Surprisingly we found that both Slit and its receptors Robo and Robo2 were actually required for migration along the VNC, 4 suggesting an attractive role with respect to hemocyte migration (compare the position of hemocytes in Fig. 2A and B).…”

“…2A and B). 4 Hemocytes remained tightly constrained within areas that are accessible to the injected dye (Fig. 2C).…”

“…2A and B). 4 However, misexpression of Slit within hemocytes failed to cause retention of hemocytes in the embryonic head, which was observed when Pvf2 was similarly misexpressed. Likewise hemocytespecific expression of Comm, a negative regulator of the Robo receptors, did not affect progression along the ventral midline, therefore it seemed that neither slit nor robo were required autonomously by hemocytes.…”

Drosophila primordial germ cell migration requires epithelial remodeling of the endoderm

“…Several recent findings hint that migrating cells in other systems might also exploit existing permeability to access new tissue environments. Mouse dendritic cells and Drosophila hemocytes appear to rely on tissue permeability and tissue remodeling, respectively, during migration (Baluk et al, 2007;Evans et al, 2010;Pflicke and Sixt, 2009). Additionally, the idea has been raised that because the vasculature within tumors is grossly compromised, it might not present an efficient barrier for cancer cell migration (Chung et al, 2010;Madsen and Sahai, 2010).…”

Epithelial delamination and migration

“…11,12 They share many characteristics with the mammalian blood cells development and function and it was hypothesized that have evolved from a common ancestor. 13,14 Drosophila hemocytes originate in the procephalic mesoderm and can be categorized into three main classes.…”