Disease relevance of Dach1

• Impaired interactions between mouse Eyal harboring mutations found in patients with branchio-oto-renal syndrome and Six, Dach, and G proteins [1].

High impact information on Dach1

• Dach transactivated a multimerized GAL4 reporter gene by coproduction of GAL4-Eya fusion proteins [2].
• Transactivation was also observed by coproduction of GAL4-Six, Eya, and Dach, indicating that Eya and Dach synergy is relevant when Eya is tethered to DNA through Six protein [2].
• Six1 is a member of the Six family homeobox genes, which function as components of the Pax-Six-Eya-Dach gene network to control organ development [3].
• Finally, to test the functional conservation hypothesis, we generated Dach2; Dach1 double mutant mice [4].
• Dach double mutants die after birth, similar to Dach1 homozygotes [4].

Biological context of Dach1

• Forebrain-specific promoter/enhancer D6 derived from the mouse Dach1 gene controls expression in neural stem cells [5].
• Mouse and human Dach/DACH were localized to chromosome 14E1 and 13q21.3-22, respectively, by fluorescence in situ hybridization [6].

Anatomical context of Dach1

• Dach1 was expressed in the distal mesenchyme of the early embryonic mouse limb bud and subsequently became restricted to the tips of digital cartilages [7].
• Dach1 protein was localized to postmitotic, prehypertrophic, and early hypertrophic chondrocytes during the initiation of ossification centers, but Dach1 was not expressed in growth plates that exhibited extensive ossification [7].
• Mouse Dach1 is a nuclear factor that is expressed during development in restricted areas of the central nervous system, neural crest, and limb buds [8].
• Dach1-positive cells, which were visualized with Enhanced Green Fluorescent Protein (EGFP), show similar distribution and axonal projections in the cortex and hippocampus in mutants and wild-type controls [8].
• Because fibroblast growth factors (FGF), bone morphogenetic proteins (BMP), and hedgehog molecules (Hh) regulate skeletal patterning of the limb bud and chondrocyte maturation in developing endochondral bones, we investigated the regulation of Dach1 by these growth and differentiation factors [7].

Co-localisations of Dach1

• Dach1 colocalized with Runx2/Cbfa1 in chondrocytes but not in the forming bone collar or primary spongiosa [7].

Regulatory relationships of Dach1

• BMP4-soaked beads down-regulated Dach1 expression, whereas Shh and bovine serum albumin had no effect [7].

Other interactions of Dach1

• Immunolocalization of FGFR2 and FGFR3 revealed overlap with Dach1 expression during skeletal patterning and chondrocyte maturation [7].
• In contrast, a significant expansion of Dac expression are observed in the anterior mesenchyme of the limb buds of hemimelic extra toes (Hx/+) mice [9].

Analytical, diagnostic and therapeutic context of Dach1

• Finally, in situ hybridization analysis demonstrated that Dach is expressed in similar tissues to those observed in Drosophila, including the embryonic nervous system, sensory organs, and limbs [6].

References