The BTB/POZ-ZF Transcription Factor dPLZF Is Involved in Ras/ERK Signaling During Drosophila Wing Development

Abstract

In Drosophila, broad complex, tramtrack, bric à brac (BTB)/ poxvirus and zinc finger (POZ) transcription factors are essential regulators of development. We searched the Drosophila genome for BTB/POZ-ZF domains and discovered an unknown Drosophila gene, dPLZF, which encodes an orthologue of human PLZF. We then characterized the biological function of the dPLZF via genetic interaction analysis. Ectopic expression of dPLZF in the wing induced extra vein formation during wing development in Drosophila. Genetic interactions between dPLZF and Ras or extracellular signal-regulated kinase (ERK) significantly enhanced the formation of vein cells. On the other hand, loss-of-function mutations in dPLZF resulted in a dramatic suppression of the extra and ectopic vein formation induced by elevated Ras/ERK signaling. Moreover, dPLZF activity upregulated the expression of rhomboid (rho) and spitz, which perform crucial functions in vein cell formation in the developing wing. These results indicate that dPLZF is a transcription factor controlled by the Ras/ERK signaling pathway, which is a prominent regulator of vein cell formation during wing development in Drosophila.

Broad‐complex, tramtrack, and bric‐à‐brac (BTB) proteins: Critical regulators of development

“…Drosophila PLZF ( dPLZF ) was only recently identified through a genome analysis as orthologous to human PLZF , with 32% sequence identity and 44% similarity over the BTB domain and seven C‐terminal ZF motifs (Maeng et al, ). Overexpression of human Plzf or dPLZF in the wing results in the formation of ectopic veins, suggesting functional conservation between the human and fly proteins (Ko et al, ; Maeng et al, ).…”

“…Drosophila PLZF ( dPLZF ) was only recently identified through a genome analysis as orthologous to human PLZF , with 32% sequence identity and 44% similarity over the BTB domain and seven C‐terminal ZF motifs (Maeng et al, ). Overexpression of human Plzf or dPLZF in the wing results in the formation of ectopic veins, suggesting functional conservation between the human and fly proteins (Ko et al, ; Maeng et al, ). While ectopic wing vein formation was enhanced by the co‐overexpression of dPLZF and members of the Ras/MAPK signaling pathway, loss of function mutations in dPLZF suppressed ectopic wing vein induction in flies overexpressing Ras , dRaf , and ERK (Maeng et al, ).…”

Concise Review: Balancing Stem Cell Self-Renewal and Differentiation with PLZF

“…In Drosophila , the PLZF ortholog tramtrack is expressed downstream of Notch signaling in the peripheral nervous system, to control the differentiation of sensory organ precursor cells (neural progenitors) into neurons or glial cells . Transgenic Drosophila strains expressing PLZF exhibit phenotypic changes by regulating ERK signaling in eye neural progenitors and wing appendage development . In mice, loss‐of‐function mutations in PLZF cause severe skeletal defects and genital hypoplasia .…”

Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors

“…Zbtb16 , among its diverse activities, controls spermatogonial stem cell renewal, and the translocation of this gene to the Rara locus is a causative transformation event in acute myeloid leukemia (214). Caenorhabditis elegans EOR-1 (215) and Drosophila CG6792 (216) have been identified as mammalian PLZF orthologs, indicating the likely origin of mammalian PLZF in bilaterians. The two protostome genes are regulated by RAS/ERK signaling during development, paralleling the direct RAS-EGR2 induction of PLZF in iNKT cell development in rodents (104).…”