The homeodomain transcription factor Orthopedia is involved in development of the Drosophila hindgut

Abstract

Background The Drosophila hindgut is commonly used model for studying various aspects of organogenesis like primordium establishment, further specification, patterning, and morphogenesis. During embryonic development of Drosophila, many transcriptional activators are involved in the formation of the hindgut. The transcription factor Orthopedia (Otp), a member of the 57B homeobox gene cluster, is expressed in the hindgut and nervous system of developing Drosophila embryos, but due to the lack of mutants no functional analysis has been conducted yet. Results We show that two different otp transcripts, a hindgut-specific and a nervous system-specific form, are present in the Drosophila embryo. Using an Otp antibody, a detailed expression analysis during hindgut development was carried out. Otp was not only expressed in the embryonic hindgut, but also in the larval and adult hindgut. To analyse the function of otp, we generated the mutant otp allele otpGT by ends-out gene targeting. In addition, we isolated two EMS-induced otp alleles in a genetic screen for mutants of the 57B region. All three otp alleles showed embryonic lethality with a severe hindgut phenotype. Anal pads were reduced and the large intestine was completely missing. This phenotype is due to apoptosis in the hindgut primordium and the developing hindgut. Conclusion Our data suggest that Otp is another important factor for hindgut development of Drosophila. As a downstream factor of byn Otp is most likely present only in differentiated hindgut cells during all stages of development rather than in stem cells.

Regulatory modules mediating the complex neural expression patterns of the homeobrain gene during Drosophila brain development

“…Several transcription factors were identified that are important for the proliferation of type I and type II neuroblasts in the brain, leading to an expansion of the brain region compared with the ventral nerve cord [ 17 ]. They include Earmuff (Erm), belonging to the FEZ family of C2H2 Zinc finger transcription factors [ 18 ], Tailless (Tll), a nuclear receptor transcription factor [ 19 ], the T-box transcription factors Doc1/2/3 [ 20 ] as well as the three homeodomain transcription factors Orthopedia (Otp) [ 21 , 22 ], Drosophila Retinal homeobox (DRx) [ 23 , 24 ] and Homeobrain (Hbn) [ 25 , 26 ], clustered in the 57B region on the second chromosome. Mutants of all these factors alone or in combination show a reduction of neuroblasts and the proliferation of their daughter cells in the embryonic brain.…”

Orthopedia expression during Drosophila melanogaster nervous system development and its regulation by microRNA-252

“…The Drosophila orthopedia (otp) gene codes for a homeodomain transcription factor (Simeone et al, 1994;Hildebrandt et al, 2020) and is a member of the 57B homeobox gene cluster together with Drosophila Retinal homeobox (DRx) (Eggert et al, 1998;Davis et al, 2003) and homeobrain (hbn) (Walldorf et al, 2000;Kolb et al, 2021). All three transcription factors are expressed in type I and type II neuroblasts in the brain and are important for progenitor cell proliferation leading to an expansion of the brain region compared with the ventral nerve cord (Curt et al, 2019).…”

“…In vertebrates orthologs have been identified in zebrafish (Del Giacco et al, 2008), chicken (Simeone et al, 1994;Caqueret et al, 2005), mouse (Simeone et al, 1994) and human (Lin et al, 1999). In the Drosophila embryo Otp is expressed in the nervous system and the hindgut, and otp mutant alleles show a severe hindgut phenotype with a complete loss of the large intestine and a reduction of the anal pads (Hildebrandt et al, 2020). This hindgut phenotype, which is due to apoptosis in the developing hindgut, leads to embryonic lethality of otp mutant alleles (Hildebrandt et al, 2020).…”

“…In the Drosophila embryo Otp is expressed in the nervous system and the hindgut, and otp mutant alleles show a severe hindgut phenotype with a complete loss of the large intestine and a reduction of the anal pads (Hildebrandt et al, 2020). This hindgut phenotype, which is due to apoptosis in the developing hindgut, leads to embryonic lethality of otp mutant alleles (Hildebrandt et al, 2020).…”

Functional analysis of enhancer elements regulating the expression of the Drosophila homeodomain transcription factor DRx by gene targeting

“…More recently, it was shown that DRx is also one of several transcription factors that are expressed in type II neuroblasts in the embryonic brain and important for progenitor cell proliferation leading to an expansion of the brain region compared with the ventral nerve cord [ 39 ]. Homeodomain transcription factors such as Orthopedia (Otp) [ 40 , 41 ] and Homeobrain (Hbn) [ 42 , 43 ] belong to these factors and are together with DRx encoded next to each other in the 57B region on the second chromosome [ 42 ]. Mutants of all these factors alone or in combination show a reduction in neuroblasts and the proliferation of their daughter cells.…”