OTX Genes in Adult Tissues

Abstract

OTX homeobox genes have been extensively studied for their role in development, especially in neuroectoderm formation. Recently, their expression has also been reported in adult physiological and pathological tissues, including retina, mammary and pituitary glands, sinonasal mucosa, in several types of cancer, and in response to inflammatory, ischemic, and hypoxic stimuli. Reactivation of OTX genes in adult tissues supports the notion of the evolutionary amplification of functions of genes by varying their temporal expression, with the selection of homeobox genes from the "toolbox" to drive or contribute to different processes at different stages of life. OTX involvement in pathologies points toward these genes as potential diagnostic and/or prognostic markers as well as possible therapeutic targets.

Keywords: OTX homeobox genes; adult tissues; inflammation; ischemia; tumor.

Figure 1

(A) Similarity alignment of OTX1 and OTX2 proteins. Red boxes represent high similarity protein sequence elaborated using COBALT Constraint-based Multiple Alignment Tool (NCBI). Black boxes represent the Homeobox domain common to the two transcription factors, small boxes the nucleotides involved in the DNA binding. (B) Interactors of OTX1 and OTX2 elaborated with STRING Version 12 software “https://string-db.org/ (accessed on 16 November 2023)”. Network nodes represent proteins, colored nodes represent query proteins (OTX1, 2) and first shell of interactors. The filled nodes indicate when a 3D structure is known or predicted. Edges represent protein–protein associations. The list of interactors has been generated using BioGRID version 4.4.225 “https://thebiogrid.org (accessed on 16 November 2023)”. Only interactors with physical, non-redundant high-throughput (HTP) evidence have been considered.

Figure 2

Schematic representation of OTX transcription factors involvement in development and differentiation in different organs.

Figure 3

Schematic representation of OTX transcription factors’ involvement in pathological diseases. Red arrows indicate the effect of upregulation or downregulation of specific effectors. Interactions with other proteins are specifically indicated in different pathologic conditions. OTX1 and OTX2 often act on the same pathway and inside the same cell system, either forming dimers or complexes with other proteins.

Figure 4

Confocal images showing immunohistochemical localization of OTX1 and OTX2 in longitudinal muscle myenteric plexus (LMMP) whole-mount preparations of the rat small intestine and colon after DNBS-induced colitis. (A–F) Co-localization of OTX1 with the glial marker S100 β. (G–L) Co-localization of OTX2 with the pan neuronal marker HuC/D. Arrows indicate neurons and asterisks indicate glial cells. With modifications from Bistoletti et al., 2020 [74]. Bar: 50 μm.