Upregulation of the Drosophila Friend of GATA Gene u-shaped by JAK/STAT Signaling Maintains Lymph Gland Prohemocyte Potency

Abstract

Studies using Drosophila melanogaster have contributed significantly to our understanding of the interaction between stem cells and their protective microenvironments or stem cell niches. During lymph gland hematopoiesis, the Drosophila posterior signaling center functions as a stem cell niche to maintain prohemocyte multipotency through Hedgehog and JAK/STAT signaling. In this study, we provide evidence that the Friend of GATA protein U-shaped is an important regulator of lymph gland prohemocyte potency and differentiation. U-shaped expression was determined to be upregulated in third-instar lymph gland prohemocytes and downregulated in a subpopulation of differentiating blood cells. Genetic analyses indicated that U-shaped maintains the prohemocyte population by blocking differentiation. In addition, activated STAT directly regulated ush expression as evidenced by results from loss-and gain-of-function studies and from analyses of the u-shaped hematopoietic cis-regulatory module. Collectively, these findings identify U-shaped as a downstream effector of the posterior signaling center, establishing a novel link between the stem cell niche and the intrinsic regulation of potency and differentiation. Given the functional conservation of Friend of GATA proteins and the role that GATA factors play during cell fate choice, these factors may regulate essential functions of vertebrate hematopoietic stem cells, including processing signals from the stem cell niche.

Serpent, Suppressor of Hairless and U-shaped are crucial regulators of hedgehog niche expression and prohemocyte maintenance during Drosophila larval hematopoiesis

“…A reduction in ush function also culminated in a robust production of lamellocytes in the lymph glands (Fig. 5H) owing to its proven function as a positive regulator of prohemocyte maintenance and as a negative regulator of lamellocyte differentiation Gao et al, 2009). …”

“…By contrast, the third lymph gland domain -the cortical zone -solely contains differentiating and mature hemocytes, such as plasmatocytes and crystal cells. Upon wasp parasitization, or in certain altered genetic backgrounds, lamellocytes will also appear in the cortical zone as a third type of differentiated hemocyte (Lanot et al, 2001;Sorrentino et al, 2002;Sorrentino et al, 2007;Gao et al, 2009;Markus et al, 2009;Tokusumi et al, 2009b).…”

Ontogeny of the Drosophila larval hematopoietic organ, hemocyte homeostasis and the dedicated cellular immune response to parasitism

“…Since in absence of PSC, no lamellocytes differentiate after wasp infestation, it indicated that the maintenance of a pool of multipotent progenitors in the MZ is a prerequisite for Drosophila larvae to be able to mount a dedicated cellular response against parasites (Crozatier et al, 2004;Krzemien et al, 2007). The Friend of GATA protein U-shaped has now to been shown to act downstream of JAK/STAT signalling to preserve pro-hemocyte potency (Gao et al, 2009). In the second report, (Mandal et al, 2007) used Antp mutants which lack Col expression in the PSC to assess the role of the PSC in 3rd instar larvae.…”

U-shaped Gene Induced by Ecdysone Signal Pathway in Drosophila

“…The Drosophila ush protein contains 1191 amino acids and 9 zinc finger domain, it can interact with srpNC to regulate the fetal hemocytes differentiation [5]. During the larval stage, ush gene only express during third instar larvae [6]. After Drosophia ush gene was knocked down, the Drosophia lamellocytes number in lymph gland increased significantly, caused lymph gland enlargement, those results indicate that ush can suppress lamellocytes differentiate into other hemocytes [7].…”

“…However, some reseach indicated that the knock down of drosophila ush gene resulting in the prohemocytes numbers decreased, and the increased expression of ush gene suppressed crystal cells and plasmatocytes differentiation. Ush can suppressed prohemocytes differentiation and maintain the prohemocytes numbers in lymph gland [9].…”