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Homeobox protein Nkx-2.2 (Gene Nkx2.2) Homo SapiensThe Nkx2-2 (map locus: 20p11.22) gene product, homeobox protein Nkx2.2, is a 273 AA (30.1 kDa) NK2 family transcription factor that contains a 60 AA (128 to 187) DNA binding homeobox. The protein contains two nuclear localization signals (NLS) that function cooperatively; KKRKRR and RYKMKRAR, Hessabi B, et al. (2000). Nkx2.2, Nkx6.1 and Irx3 are part of a homeodomain protein combinatorial code that specifies progenitor cell identity and neuronal fate in the ventral neural tube, Briscoe J, et al (2000). Nkx2.2 is expressed in the ventral midline domains of neuroectoderm (neural tube), Weiss JB, et al. (1998), during early development where its expression requires sonic hedgehog (Shh) signaling, Pabst O. et al. (2000). Nkx2-2 is required for the establishment of the dopaminergic progenitor domain in mammalian ventral midbrain, Prakash N and Wurst W, (2007) and serotonergic (5-HT) neurons in the brainstem and ventral spinal cord, Cheng L, et al. (2003). Nkx2.2 is selectively expressed in oligodendrocyte progenitors (OPC) that arise from glial precursors located in the ventral neural tube. Nkx2.2 has emerged as a key regulator of oligodendrocyte differentiation. It regulates the differentiation and/or maturation, but not the initial specification of oligodendrocyte progenitors, Qi Y, et al. (2001). Oligodendrocytes (OL) arise from Nkx2.2-expressing progenitors by a Shh-dependent mechanism, Soula C, et al. (2001). Coexpression of Olig2 (a bHLH transcription factor) and Nkx2.2 in the spinal cord, Zhou Q, et al. (2001) and ventricular and subventricular zones of the midbrain, Fu H, et al. (2003) promotes oligodendrocyte differentiation, Agius E, et al. (2004), wherein both factors act as repressors, Zhou Q, et al. (2001). In addition to supporting oligodendrocyte differentiation during development, Nkx2.2 supports the generation of new oligodendrocytes and remyelination after injury to adult CNS tissues, Watanabe M, et al. (2004), Fancy SP, et al. (2004). Nkx2.2 is involved in the differentiation of endocrine cell types within the pancreas. It is required for the differentiation of insulin-producing beta-cells, Sander M, et al. (2000), Wang J, et al. (2004) and most of the glucagon-producing alpha-cells, Prado CL, et al. (2004). In addition, it represses the differentiation of epsilon (ghrelin-secreting) pancreatic cells, Pauls S, et al. (2007). Nkx2.2 is required for mature beta-cell function and islet structure, Doyle MJ and Sussel L. (2007). Nkx2.2 promotes differentiation of ES stem cells into insulin-producing cells, Shiroi A, et al. (2005). Nkx2.2 is expressed at the onset of intestinal epithelial cell differentiation where it supports hormone-producing enteroendocrine cell differentiation, Desai S, et al. (2008) and taste bud cells, Miura H, et al. (2003). Nkx2.2 is emerging as a marker for oncogenic transformation of Ewing’s sarcoma where its presence correlates with a poor prognosis, Smith R, et al. (2006), Owen LA, et al. (2008), Cheung IY, et al. (2007). Sigma offers antibodies and shRNAs useful for the study of Nkx2.2 gene products. References: Briscoe J, et al. (2000) A homeodomain protein code specifies progenitor cell identity and neuronal fate in the ventral neural tube. Cell. 101: 435-445. |
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