{"id":978,"date":"2025-12-02T17:23:52","date_gmt":"2025-12-02T17:23:52","guid":{"rendered":"http:\/\/littleheroesfoundation.org\/?p=978"},"modified":"2025-12-02T17:23:52","modified_gmt":"2025-12-02T17:23:52","slug":"c-da-gal4-uas-lat-ubiquitous-expression-of-lat-detected-by-lacz-immunostaining","status":"publish","type":"post","link":"https:\/\/littleheroesfoundation.org\/?p=978","title":{"rendered":"\ufeff(C) da-Gal4; UAS-Lat ubiquitous expression of Lat detected by LacZ immunostaining"},"content":{"rendered":"

\ufeff(C) da-Gal4; UAS-Lat ubiquitous expression of Lat detected by LacZ immunostaining. theDrosophilatype I cytokine signalling receptor related to mammalian GP130, and antagonises Domeless activity in a dose-dependent manner. Our analysis further shows that a primary immune response to wasp parasitism is a strong decrease in cytokine mRNA levels in the lymph gland, followed by an increase in thelatran\/domelessratio. We propose that this sequence of events culminates in the complete inhibition of residual JAK\/STAT signalling by Latran. JAK\/STAT activity has been associated with several human diseases including leukaemia while knock-out studies in mice point to a central role of this pathway in hematopoiesis and regulation of immune functions. The specific function ofDrosophilaLatran is, to our knowledge, the first in vivo example of a role for a nonsignalling receptor in controlling a dedicated immune response, and thus raises the question of whether short, nonsignalling receptors also control specific aspects of vertebrate cellular immunity. == Author Summary == A specific microenvironment termed the niche supports long term maintenance of hematopoietic stem cells in vertebrates. A small group of specialised cells called the posterior signalling center (PSC) controls hemocyte (blood cell) homeostasis in theDrosophilalarval hematopoietic tissue and thus fulfills a similar function to the vertebrate niche. The PSC acts at a distance to maintain JAK\/STAT signalling in hematopoietic progenitors (prohemocytes), thereby ensuring their multipotent character. We report here that a short cytokine receptor encoded byCG14225\/latranis required to extinguish JAK\/STAT signalling in prohemocytes and thereby ensures their mass differentiation into lamellocytes, STF 118804 an immune cell type required to fight specific threats such as wasp parasitism. Domeless, a related receptor inDrosophila, was previously the only known cytokine receptor that signals through the JAK\/STAT pathway. We show that Latran lacks the intracellular domains required for signal transduction and acts instead by antagonizing the function of Domeless in a dose-dependent manner. The role ofDrosophilaLatran in the repression of JAK\/STAT signalling under specific immune conditions raises the question of whether short, nonsignalling receptors that antagonize full-length receptors could also control specific aspects of vertebrate immunity. == Introduction == The innate immune responsethe synthesis of antimicrobial peptides and mobilisation of dedicated immune cellsconfers a broad protection against pathogens to all multicellular organisms.Drosophilahas become a model for studying the role of hematopoietic (blood) cells and the evolution of cellular immunity (reviews by[1],[2]). Similar to vertebrates,Drosophilahematopoiesis occurs in two waves during development[3]. A first population of hemocytes is specified in the embryo and gives rise to plasmatocytes involved in phagocytosis and crystal cells required for melanisation[4]. A second wave of plasmatocyte and crystal cell production occurs at the end of larval development. Larval hematopoiesis can also give rise to a third cell type, the lamellocytes, which are devoted to the encapsulation of foreign bodies too large to be phagocytosed. Lamellocytes only differentiate in response to specific immune challenges such as parasitisation by wasps, STF 118804<\/a> a common threat for higher order insects[1],[2],[5],[6]. Larval hematopoiesis takes place in a specialised organ, the lymph gland (LG), which forms during embryogenesis and grows during larval development. In third instar larvae, the LG is composed of several STF 118804 lobes with the anterior-most lobes organised into a medullary zone (MZ) containing Mouse monoclonal to NFKB1<\/a> the hematopoietic progenitors, a cortical zone (CZ) containing differentiating hemocytes, and a so-called posterior signalling centre (PSC) (Figure 1F)[7]. These three zones can be identified by the expression of different markers. Differentiating crystal cells and plasmatocytes in the CZ express prophenoloxidase (proPO) and the P1 Nimrod receptor[8], respectively. Hematopoietic progenitors can be distinguished by their expression ofdomeless(dome), which encodes theDrosophilareceptor of the janus tyrosine kinase\/signal transducers and activators of transcription (JAK\/STAT) pathway andtep4, which encodes a thioester protein[7],[9]. PSC cells express the transcription factors Antennapedia (Antp) and Collier\/Knot (Col), theDrosophilaEarly B-cell Factor (EBF) ortholog[10], and the morphogen Hedgehog (Hh)[7],[11][13]. The PSC controls the balance between multipotent prohemocytes present in the MZ and differentiating hemocytes[9],[12]. It acts in a noncell-autonomous manner, perhaps via Hh signalling, to maintain JAK\/STAT signalling in prohemocytes, thus preserving the multipotent character necessary for these cells to adopt a lamellocyte fate upon parasitisation. This key role of the PSC revealed that, inDrosophila, larval hemocyte homeostasis is dependent upon interactions between hematopoietic progenitors and their micro-environment, a role reminiscent of the vertebrate hematopoietic market[9],[12],[14]. == Physique 1. Latran: homology with JAK\/STAT receptors and manifestation in the LG. == (A) Schematic of theD. melanogasterdome-lat genomic region. The ORFs and untranslated 5 and 3 areas are indicated by black and.<\/p>\n","protected":false},"excerpt":{"rendered":"

\ufeff(C) da-Gal4; UAS-Lat ubiquitous expression of Lat detected by LacZ immunostaining. theDrosophilatype I cytokine signalling receptor related to mammalian GP130, and antagonises Domeless activity in a dose-dependent manner. Our analysis further shows that a primary immune response to … <\/p>\n

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