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Homeobox protein Nkx-6.1 (Gene Nkx6.1) Homo SapiensThe NKX6-1 (map locus 4q21.2-q22, Inoue H, et al. (1997); Ensembl 4q21.23, HGNC 4q21.33) gene product, homeobox protein Nkx-6.1, is a 367 AA (37.8 kDa) transcription factor that contains a 60 AA (236-295) DNA-binding homeobox. Nkx6 homeodomain transcription factors have important developmental roles in the CNS and the pancreas. Nkx6.1 is essential for proper motoneuron and oligodendrocyte development and the development and maintenance of insulin-producing pancreatic beta cells. Nkx-6.1 is expressed in ventral neural progenitor cells and subsequently in the median half of the lateral motor neuron column (LMCm) and in mesenchymal tissues surrounding Shh-expressing cells; ventral spinal meninges, esophageal mesenchyme, and dorsal tracheal mesenchyme, Cai J, et al. (2000). Nkx6.1 is induced by axial mesendoderm and Shh in the mantle zone along with Islet-1 in a subset of motor neurons. BMP-7 represses Nkx-6.1 expression, Qiu M et al. (1998). Nkx6.1 is required for ventral regional patterning and neuronal fate determination in the vertebrate CNS. Nkx6.1 controls motor neuron and ventral interneuron fates, Sander M, et al. (2000). Nkx6.1 controls migration and axon pathfinding of cranial branchio-motoneurons, Muller M, et al. (2003) and it is required for the early specification of somatic motoneuron progenitors in the spinal cord. Early specification of branchio-motoneurons (hindbrain) is independent of Nkx6.1 function, but it is required for their subsequent development. Nkx6.1 is required for the development of postmitotic motoneurons, and the control of branchio-motoneuron migration, Muller M, et al. (2003). The status of Nkx6.1 expression in certain motor neuron pools regulates muscle nerve formation, and the pattern of innervation of individual muscles, De Marco Garcia NV and Jessell TM, (2008). Nkx6.1 and Nkx6.2 also regulate the differentiation of oligodendrocytes in the spinal cord and hindbrain. These factors promote oligodendrocyte differentiation in the ventral spinal cord and inhibit it in the anterior hindbrain, Vallstedt A, et al. (2005). Nkx6.1 is recognized as the most beta-cell specific transcription factor in the pancreas, Pedersen IL, et al. (2006). It is expressed in both developing and mature beta-cells. Nkx6.1, which is expressed downstream of Nkx2.2, is prevalent during the secondary transition (late maturation) wave of beta-cell differentiation that leads to insulin-producing cells, Sander M, et al. (2000), Nielsen K, et al. (2004). Nkx6.1 suppresses glucagon expression and regulates glucose-stimulated insulin secretion in islet beta cells, Schisler JC, et al. (2005). Its ability to suppress glucagon gene expression has been linked to interference with Pax6 binding to the glucagon promoter, Gautier BR, et al. (2007). A potential use of Nkx6.1 as a therapeutic agent for diabetes has been recognized based on its unique ability to stimulate beta-cell replication with retention or enhancement of function, Schisler JC, et al. (2008). Sigma offers antibodies and shRNAs useful for the study of Nkx6.1 gene products. References: Cai J, et al. (2000) Evidence for the differential regulation of Nkx-6.1 expression in the ventral spinal cord and foregut by Shh-dependent and -independent mechanisms. Genesis. 27: 6-11. |
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