The POU Transcription Factor Drifter/Ventral veinless Regulates Expression of Drosophila Immune Defense Genes

Abstract

Innate immunity operates as a first line of defense in multicellular organisms against infections caused by different classes of microorganisms. Antimicrobial peptides (AMPs) are synthesized constitutively in barrier epithelia to protect against microbial attack and are also upregulated in response to infection. Here, we implicate Drifter/Ventral veinless (Dfr/Vvl), a class III POU domain transcription factor, in tissue-specific regulation of the innate immune defense of Drosophila. We show that Dfr/Vvl is highly expressed in a range of immunocompetent tissues, including the male ejaculatory duct, where its presence overlaps with and drives the expression of cecropin, a potent broad-spectrum AMP. Dfr/Vvl overexpression activates transcription of several AMP genes in uninfected flies in a Toll pathway-and Imd pathway-independent manner. Dfr/Vvl activates a CecA1 reporter gene both in vitro and in vivo by binding to an upstream enhancer specific for the male ejaculatory duct. Further, Dfr/Vvl and the homeodomain protein Caudal (Cad) activate transcription synergistically via this enhancer. We propose that the POU protein Dfr/Vvl acts together with other regulators in a combinatorial manner to control constitutive AMP gene expression in a gene-, tissue-, and sex-specific manner, thus promoting a first-line defense against infection in tissues that are readily exposed to pathogens.

Schwann cells and their transcriptional network: Evolution of key regulators of peripheral myelination

“…2). The single SoxE subfamily member Sox100B in Drosophila melanogaster is primarily involved in gonadal development and somatic testis differentiation (DeFalco et al, 2003;Nanda et al, 2009), while the single class III POU domain protein Cf1a/Drifter/Ventral Veinless functions during vein, tracheal, wing and neuronal development as well as in the innate immune defense (Anderson et al, 1995;de Celis et al, 1995;Junell et al, 2010). Given the fact that factors in each subgroup were dramatically increased in number during vertebrate evolution, it seems likely that these additional SoxE and class III POU domain proteins were "in search" of function.…”

Immune Response in the Barrier Epithelia: Lessons from the Fruit Fly <i>Drosophila melanogaster</i>

“…tub), midgut and hindgut are labelled [60] . d Constitutive Cec-GFP expression in the ejaculatory duct of an uninfected male [26] . acc.…”

“…These include Cec, Att , Drs and Andropin, primarily in the ejaculatory duct ( fig. 1 d) [18,25,26,28] . In addition to the widespread constitutive and inducible expression of AMPs in barrier epithelial tissues, each tissue also has its own distinctive immune response, which we will attempt to address below.…”

“…This expression does not involve NF-B/Rel and GATA transcription factors. Instead, the homeobox transcription factor Caudal (Cad) and the POU domain transcription factor Ventral Veinless (Vvl) were shown to bind to tissue-specific enhancers and promote the expression of Drs and Cec in salivary glands and reproductive organs in uninfected, healthy flies [25,26] . Sex-based differences in AMP expression are apparent within the genital organs of Drosophila.…”

“…Direct exposure to Pseudomonas aeruginosa led to expression of some IMD-, JNK-and Janus kinase (JAK)/signal transducer and activator of transcription (STAT)-responsive genes, suggesting a role for all of these pathways in tracheal immunity. Among the genes that were induced in tracheal tissues upon infection is vvl, a transcription factor that is present in many immune-competent tissues and was recently shown to play a role in the regulation of CecA1 expression [26] . Vvl most likely acts with other regulators to control expression of AMP genes in a tissue-specific manner.…”