Disease relevance of repo

• Subsequent to the laminar cell death, the retinal cells in the repo visual system also degenerated, indicating that the retinal cell death was due to retrograde degeneration [1].
• Embryos mutant for the gene encoding RK2 are embryonic lethal but normal for early gliogenesis (birth, initial divisions and migration of glia) and axonogenesis (neuronal pathfinding and fasciculation) [2].
• By using a glia-specific marker (antibody against the Repo protein) we have reconstructed the pattern of glial cell precursors at successive developmental stages, focusing on the glia of the supraesophageal ganglion and subesophageal ganglion which are not described in previous studies [3].

High impact information on repo

• Weak repo alleles were viable but affected glia in the optic lobe, resulting in a reversal in polarity of the electrophysiological to light in the adult [4].
• The repo gene encoded a homeo domain protein suggesting that it might be a transcriptional regulator of genes required for glial development [4].
• In the adult visual system, repo was expressed in laminal glia, medullar glia, and subretinal cells; in the embryo, repo was expressed in nearly all of the identified glia in the central and peripheral nervous systems except midline glia [4].
• The repo glia also underwent cell death, suggesting that the laminar neurons are required for survival of the glia or that repo expression is required to suppress an intrinsic cell suicide program [1].
• Defective glia induce neuronal apoptosis in the repo visual system of Drosophila [1].

Biological context of repo

• Multiple Gcm binding sites are found in repo upstream DNA [5].
• By ectopically expressing Repo, we show that Repo can regulate its own enhancer [5].
• Correspondingly, in loss-of-function repo mutants, whose glial cells also fail to differentiate, photoreceptor axons showed the impaired projection pattern similar to the argos phenotype [6].
• The role of glia in suppressing neuronal cell death was investigated in the visual system of the Drosophila mutant, reversed polarity (repo) [1].
• The homeobox gene repo is required for the differentiation and maintenance of glia function in the embryonic nervous system of Drosophila melanogaster [7].

Anatomical context of repo

• Eleven such GCM-binding sequences are found in the 5' upstream region of the repo gene, whose expression in early glial cells is dependent on gcm [8].
• However, while repo is expressed in Gcm positive glia, it is not expressed in Gcm positive hemocytes [5].
• RK2 is absent from skeletal muscle whereas RK1 and RK3 are present in this tissue [9].

Regulatory relationships of repo

• In Drosophila lateral glial cell development is initiated by the transcription factor encoded by glial cells missing. glial cells missing activates downstream transcription factors such as repo and pointed which subsequently control terminal glial differentiation [10].
• We further find that jing is required for neuronal and glial survival as repo- and castor-expressing cells undergo cell death in homozygous jing (3) mutant embryos, as revealed by double labeling with Tunel [11].

Other interactions of repo

• This suggests that the GCM protein is a transcriptional regulator directly controlling repo [8].
• In different types of glial cells, REPO can act alone, or cooperate with either TTK69 or PNTP1 to regulate different target genes [12].
• Expression of biparous is not observed in end stage postmitotic neurons and precedes the expression of repo, a gene activated in later stages of glial differentiation [13].
• We found that nearly all lgl micrometastases co-express the neuronal cell marker, ELAV, and the glial cell marker, REPO [14].

References