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MicroRNAs are an important class of gene expression regulators that are involved in many biological processes including embryogenesis. miR-125b is a conserved microRNA that is enriched in the nervous system. We have previously reported the function of miR-125b in neuronal differentiation of human cell lines. We also discovered the function of miR-125b in regulating p53 in human and zebrafish. Here we further characterize the brain defects in zebrafish embryos injected with morpholinos against miR-125b. Our data confirm the essential role of miR-125b in brain morphogenesis particularly in maintaining the balance between proliferation, cell death and differentiation. We identified lunatic fringe (lfng) as an additional target of miR-125b in human and zebrafish and suggest that lfng may mediate the function of miR-125b in neurogenesis. Together, this report reveals new insights into the function of miR- 125b during neural development of zebrafish., {"references":["D. P. Bartel, \"MicroRNAs: genomics, biogenesis, mechanism, and\nfunction,\" Cell, vol. 116, pp. 281-297, 2004.","B. Ason, et al., \"From the Cover: Differences in vertebrate microRNA\nexpression,\" Proc.Natl.Acad.Sci.U.S.A, vol. 103, pp. 14385-14389, 2006.","M. Selbach, et al., \"Widespread changes in protein synthesis induced by\nmicroRNAs,\" Nature, vol. 455, pp. 58-63, 2008.","P. H. Olsen and V. Ambros, \"The lin-4 regulatory RNA controls\ndevelopmental timing in Caenorhabditis elegans by blocking LIN-14\nprotein synthesis after the initiation of translation,\" Dev.Biol., vol. 216,\npp. 671-680, 1999.","E. E. Caygill and L. A. Johnston, \"Temporal regulation of metamorphic\nprocesses in Drosophila by the let-7 and miR-125 heterochronic\nmicroRNAs,\" Curr.Biol., vol. 18, pp. 943-950, 2008.","E. A. Miska, et al., \"Microarray analysis of microRNA expression in the\ndeveloping mammalian brain,\" Genome Biol., vol. 5, p. R68, 2004.","L. Smirnova, et al., \"Regulation of miRNA expression during neural cell\nspecification,\" Eur.J.Neurosci., vol. 21, pp. 1469-1477, 2005.","L. F. Sempere, et al., \"Expression profiling of mammalian microRNAs\nuncovers a subset of brain-expressed microRNAs with possible roles in\nmurine and human neuronal differentiation,\" Genome Biol., vol. 5, p.\nR13, 2004.","E. Wienholds, et al., \"MicroRNA expression in zebrafish embryonic\ndevelopment,\" Science, vol. 309, pp. 310-311, 2005.\n[10] M. T. Le, et al., \"MicroRNA-125b promotes neuronal differentiation in\nhuman cells by repressing multiple targets,\" Mol Cell Biol, vol. 29, pp.\n5290-305, Oct 2009.\n[11] M. T. Le, et al., \"MicroRNA-125b is a novel negative regulator of p53,\"\nGenes Dev, vol. 23, pp. 862-76, Apr 1 2009."]}

Transforming growth factor-beta (TGF-beta) affects multiple cellular functions through the type I and type II receptor Ser/Thr kinases (TbetaRI and TbetaRII). Analysis of TGF-beta signaling pathways has been hampered by the lack of cell lines in which both TbetaRI and TbetaRII are deleted, and by the inability to study signal transduction by TbetaRI independently of TbetaRII since TbetaRI does not bind TGF-beta directly. To overcome these problems, we constructed and expressed chimeric receptors with the extracellular domain of the erythropoietin receptor (EpoR) and the cytoplasmic domains of TbetaRI or TbetaRII. When expressed in Ba/F3 cells, which do not express EpoR, Epo induces the formation of a heteromeric complex between cell surface EpoR-TbetaRI and EpoR-TbetaRII chimeras. Neither the EpoR-TbetaRI nor the EpoR-TbetaRII chimera interacts with endogenous TGF-beta receptors. Ba/F3 cells expressing both EpoR-TbetaRI and EpoR-TbetaRII chimeras, but not EpoR-TbetaRI or EpoR-TbetaRII alone, undergo Epo-induced growth arrest. When expressed in Ba/F3 cells in the absence of the EpoR-TbetaRII chimera, EpoR-TbetaRI(T204D), a chimeric receptor with a point mutation in the GS domain of TbetaRI that is autophosphorylated constitutively, triggers growth inhibition in response to Epo. Thus, both homo- and heterodimerization of the cytoplasmic domain of the type I TGF-beta receptor are required for intracellular signal transduction leading to inhibition of cell proliferation. These chimeric receptors provide a unique system to study the function and signal transduction of individual TGF-beta receptor subunits independently of endogenous TGF-beta receptors.