Disease relevance of Otx1

• Otx1-/- mice showed spontaneous epileptic behaviour and multiple abnormalities affecting mainly the telencephalic temporal and perirhinal areas, the hippocampus, the mesencephalon and the cerebellum, as well as the acoustic and visual sense organs [1].
• In particular Otx1 null mice are viable and show spontaneous epileptic seizures and abnormalities affecting the dorsal telencephalic cortex [2].
• Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescent stage-specific control of pituitary levels of GH, FSH and LH [3].

High impact information on Otx1

• To decipher its role in vivo we produced null mice by replacing Otx1 with the lacZ gene [1].
• Expression data during murine embryogenesis and postnatal brain development support the idea that Otx1 could be required for correct brain and sense organs development [1].
• The Otx1 expression domain is similar to that of Otx2, but contained within it [4].
• In contrast, heterozygous mutants displayed craniofacial malformations designated as otocephaly; affected structures appeared to correspond to the most posterior and most anterior domains of Otx expression where Otx1 is not expressed [5].
• Following trkB deletion in pyramidal cells, their dendritic arbors are altered, and cortical layers II/III and V are compressed, after which there is an apparent loss of mutant neurons expressing the transcription factor SCIP but not of those expressing Otx-1 [6].

Biological context of Otx1

• Here, we have analysed the ocular phenotype of mice carrying different functional copies of Otx1 and Otx2 and we show that these genes are required in a dose-dependent manner for the normal development of the eye [7].
• Furthermore, in Otx1(-/-); Otx2(+/-) mice neural retina cell proliferation, cell differentiation and apoptotic cell death were also severely affected [7].
• In 12.5-day and 15.5-day embryos, the Otx2 gene expression is restricted to the nasal epithelium and its associated glands, while the Otx1 transcripts are present in both nasal and facial integuments, including nasal glands and hair vibrissa follicles [8].
• The TINS Lecture. Understanding the roles of Otx1 and Otx2 in the control of brain morphogenesis [9].
• Otx1 expression is detectable from day 8 of gestation in telencephalic, diencephalic and mesencephalic regions [10].

Anatomical context of Otx1

• Homozygous mice show a lack of large pyramidal cells in layer V of the cortex, which is reflected in a reduction in the number of Otx1-positive neurons in this layer during postnatal development [11].
• Thus, as revealed by anatomical and molecular analyses, only Otx1-/-; Otx2+/- embryos lacked mesencephalon, pretectal area, dorsal thalamus and showed an heavy reduction of the Ammon's horn, while the metencephalon was dramatically enlarged occupying the mesencencephalic area [12].
• Recently Otx1 has been found to be specifically expressed during neurogenesis of layer 5 and 6 in the developing cerebral cortex [13].
• From 1 to 3 somites stage onwards, Otx1 and Otx2 are largely coexpressed, but only Otx2 is expressed during gastrulation [14].
• Within layer 5, Otx1 is expressed by neurons with subcortical axonal projections to the midbrain and spinal cord [15].

Associations of Otx1 with chemical compounds

• Cell culture experiments indicate that Otx1 may activate transcription of the growth hormone (GH), follicle-stimulating hormone (betaFSH), luteinizing hormone (betaLH) and alpha-glycoprotein subunit (alphaGSU) genes [3].
• METHODS: The 400-microm slices were prepared from the somatosensory cortex of Otx1-/- and Otx1+/+ mice, and the current clamp intracellular recordings were obtained from layer V pyramidal neurons by means of pipettes containing K+ acetate 1.5 mol/L and biocytin 2% (pH 7.3) [16].

Regulatory relationships of Otx1

• Here, we show that Otx1 is expressed in hematopoietic pluripotent and erythroid progenitor cells [17].

Other interactions of Otx1

• Later in development, Svet1 and Otx1 were expressed in subsets of cells of upper (II-IV) and deep (V-VI) layers, respectively [18].
• 2. Finally, expression of the former genes, and Otx-1 and Emx-2, suggests that the cephalic neural plate is organized into molecularly distinct domains delimited by longitudinal and transverse borders; these results provide a foundation for defining the mechanisms that pattern the neural plate [19].
• The pattern of positivity of the GABAergic marker glutamic acid decarboxylase in Otx1(-/-) cortex was also altered and similar to that of parvalbumin [20].
• Moreover, bone marrow cells from mice lacking Otx1 exhibit a cell-autonomous impairment of the erythroid compartment [17].
• Here we report that Otx1, a homeobox-containing gene of the Otx gene family, is postnatally transcribed and translated in the pituitary gland [3].

Analytical, diagnostic and therapeutic context of Otx1

• Histological and in situ hybridization experiments of both Otx1-/- and Otx1-/-;Otx2(+/)- mutants revealed that the lateral crista was absent [21].
• RESULTS: In the present work, Otx1 null mutant mice were generated by gene targeting in embryonic stem cells [22].
• We investigated structural alterations in excitatory and inhibitory circuits in somatosensory cortex of Otx1(-/-) mice by immunocytochemistry using light, confocal and electron microscopy [20].

References