minibrain

DEVELOPMENTAL BIOLOGY

Protein extracts of embryos and pupae contain consistently more Mnb protein A and C than those of third instar larvae and adults. By contrast, Mnb protein B appears to be expressed most markedly in third instar larvae and pupae. In addition, Mnb protein B is the most prominent of the three in third instar larvae (Tejedor, 1995).

Embryonic

In late embryos, MNB mRNA is expressed in the ventral cord and in the brain, but not in the peripheral nervous system. Also, MNB mRNA is not detected in embryonic neuroblasts (Tejedor, 1995).

Larval

Anti Mnb antibodies stain most prominently the mushroom body neuropil and the opc of the optic lobes. Thus mnb appears to be expressed prominently in larval tissue where neuronal progeny are generated during post-embryonic development. Strikingly, the level of protein is low in adult optic lobes and central brain hemispheres (Tejedor, 1995)

Adult

The level of Mnb protein is low in adult optic lobes and central brain hemespheres but relatively high in retinal pigment cells and in the alpha, beta and gama lobes and peduncle of the mushroom bodies (Tejedor, 1995).

Effects of mutation or deletion

Four alleles of minibrain have been described. The external appearance of mutant flies, including body and sensory organs, is nearly indistinguishable from wild type. The mutants are slightly smaller in size and require about 10% more time for their development; they also have considerable difficulties escaping from their pupal case. The brains of adult mutant flies are greatly reduced in size but shows no gross alterations in neuronal architecture. Major size reductions are seen in the optic lobes (50%-70%), most markedly in the lobula complex and in the central brain (40%-50%). The marked reduction of the lobula complex is probably also the reason for the increased curvature of the medulla in mnb mutants. The central brain hemispheres are reduced mainly in their ventral to dorsal and, respectively, anterior and posterior extensions. Axon bundles that project from the lobula complex to the lateral protocerebrum (optic stalk) are visibly thinner in the mutants. The number of anterior optic tract fibers is reduced by about 70%, and the number of cervical connective fibers is reduced by about 30%. Eyes appear normal (Tejedor, 1995).

Freely walking mutant flies cannot fixate a pattern in an area test. Wild type flies are attracted by a vertical dark stripe surrounded by an illuminated translucent area, while mutant flies have lost this preference. Odor discrimination is poor. Although locomotor activity of freely walking animals is low, optomotor turning behavior of mutant males walking on a styrofoam ball and motion-induced landing responses are normal.

minibrain mutant larvae develop normally into the third instar. Mutations cause an abnormal spacing of neuroblasts in the outer proliferation center (opc) of larval brain, with the implication that mnb opc neuroblasts produce less neuronal progeny than do wild type. As a consequence, the adult mnb brain exhibits a specific and marked size reduction of the optic lobes and central brain hemispheres. The insufficient number of distinct neurons in mnb brains is correlated with specific abnormalities in visual and olfactory behavior, although eye and antennal morphology are normal (Tejedor, 1995).

The influence of mutations in seven neurological genes on the number of fibers in the anterior optic tract (AOT) of Drosophila melanogaster has been investigated. The number of fibers in the AOT can be drastically reduced in single and especially in multiple mutants. However, no evidence for synergistic interactions between the sample of mutations used in any of the genes examined (sine oculis , reduced optic lobes, minibrain, and small optic lobes) was obtained at the level of the AOT. The rolKS222 and so mutations eliminate similar fiber sets in the AOT, which are distinctly different from those eliminated by solKS58 and mnb1 (Hoube, 1992).

Bescond, M. and Rahmani, Z. (2005). Dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A) interacts with the phytanoyl-CoA alpha-hydroxylase associated protein 1 (PAHX-AP1), a brain specific protein. Int. J. Biochem. Cell. Biol. 37(4): 775-83. 15694837

Chen, H. and Antonarakis, S. E. (1997). Localisation of a human homologue of the Drosophila mnb and rat Dyrk genes to chromosome 21q22.2. Hum. Genet. 99 (2): 262-265.

Chen-Hwang, M. C., et al. (2002). Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A substrate. J. Biol. Chem. 277(20): 17597-604. 11877424

Deng, X., et al. (2003). Mirk/dyrk1B is a Rho-induced kinase active in skeletal muscle differentiation. J. Biol. Chem. 278(42): 41347-54. 12902328

Fotaki, V., et al. (2002). Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice. Mol. Cell. Biol. 22(18): 6636-47. 12192061

Guimera, J., et al. (1996). A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region. Hum. Mol. Genet. 5 (9): 1305-1310.

Hammerle, B., et al. (2002). Mnb/Dyrk1A is transiently expressed and asymmetrically segregated in neural progenitor cells at the transition to neurogenic divisions. Dev. Biol. 246: 259-273. 12051815

Hammerle, B., et al. (2003). Expression patterns and subcellular localization of the Down syndrome candidate protein MNB/DYRK1A suggest a role in late neuronal differentiation. Eur. J. Neurosci. 17(11): 2277-86. 12814361

Hofbauer, A. and Campos-Ortega, J. A. (1990). Proliferation pattern and early differentiation of the optic lobes in Drosophila melanogaster. Roux's Arch. Dev. Biol. 198: 264-274

Hoube, B. and Fischbach, K. F. (1992). Additive gene actions on the fiber number in the anterior optic tract of Drosophila melanogaster. J Neurogenet 8 (2): 115-123.

Kelly, P. A. and Rahmani, Z. (2005). DYRK1A enhances the mitogen-activated protein kinase cascade in PC12 cells by forming a complex with Ras, B-Raf, and MEK1. Mol. Biol. Cell 16(8): 3562-73. 15917294

Lochhead, P. A., et al. (2003). dDYRK2: a novel dual-specificity tyrosine-phosphorylation-regulated kinase in Drosophila. Biochem J. 374(Pt 2): 381-91. 12786602

Lochhead, P. A., et al. (2005). Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs. Cell 121(6): 925-36. 15960979

Pang, K. M., et al. (2004). The minibrain kinase homolog, mbk-2, is required for spindle positioning and asymmetric cell division in early C. elegans embryos. Dev. Biol. 265(1): 127-39. 14697358

Raich, W. B., et al. (2003). Characterization of Caenorhabditis elegans homologs of the Down syndrome candidate gene DYRK1A. Genetics 163(2): 571-80. 12618396

Selleck, S. B. and Steller, H. (1991). The influence of retinal innervation on neurogenesis in the first optic ganglion of Drosophila. Neuron 6: 83-99

Shindoh, N., et al. (1997). Cloning of a human homolog of the Drosophila minibrain/rat Dyrk gene from "the Down syndrome critical region" of chromosome 21. Biochem. Biophys. Res. Commun. 225 (1): 92-99.

Smith, D. J., et al. (1997). Functional screening of 2 Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome Nat. Genet. 16 (1): 28-36.

Song, W. J., et al. (1996). Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome "critical region". Genomics 38 (3): 331-339.

Tejedor, F., et al. (1995). minibrain: a new protein kinase family involved in postembryonic neurogenesis in Drosophila. Neuron 14: 287-301.

Zou, M., et al. (2003). Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial cell migration and is negatively regulated by the Met adaptor Ran-binding protein. J. Biol. Chem. 278(49): 49573-8114500717

date revised: 30 October 2005 

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