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Engrailed homolog 1 (Gene En1)Homo sapiensThe EN1 (map locus: Ensembl/HGNC: 2q14.2; Entrez: 2q13-q21, Köhler A, et al. (1993)) gene product, homeobox protein engrailed-1, is a 392 AA (40.1 kDa) homeobox transcription factor that contains a 60 AA (303-362) DNA-binding homeobox, a 20 AA (199 to 218) polyAla region and an 8 AA (224 to 231) polyGly region. Homeobox transcription factor engrailed-1 is involved in the regionalization of the central nervous system (CNS) and spinal cord and support of neuron function and survival. It is also essential for the patterning of limb development, Loomis CA, et al. (1996), aspects of craniofacial bone development, Deckelbaum RA, et al. (2006) and trunk skeletal muscle development, Ahmed MU, et al. (2006). Dysfunction of regulation or mutations in engrailed-1 may be linked to major diseases such as Autism, Kuemerle B, et al. (2007) and Parkinson’s diseases, Simon HH, et al. (2001). En1 is the earliest molecular marker of midbrain tissue, Shamim H. et al. (1999) and it is an essential gene for midbrain development and regionalization. It is expressed in all neuronal groups of the medulla and throughout the cerebellum including cerebellar granule cell layers, white matter of the vermis and flocculus, inferior olive, arcuate nucleus, caudal raphe nuclei, corpus pontobulbare and nucleus ambiguus, Zec N, et al. (1997). The role of En-1 in cerebellar development has been discussed recently by Murcia CL, et al. (2007). En-1 is also involved in regionalization of the optic tectum, Nakamua H, et al. (2001). En-1 may play an important role in understanding and future therapies for Parkinson’s disease. En-1 is involved in generation and/or survival of mid-hindbrain precursor cells, Wurst W, et al. (1994) and it is highly expressed by essentially all dopaminergic neurons in the substantia nigra compacta (SNc) and ventral tegmentum, Simon HH, et al. (2001). En-1 and En-2 regulate expression of alpha-synuclein, a gene that is genetically linked to Parkinson's disease. Engrailed genes are expressed by midbrain dopaminergic neurons from their generation to adulthood but are not required for their specification. Engrailed genes control the survival of midbrain dopaminergic neurons in a gene dose-dependent manner, Simon HH, et al. (2001). Engrailed genes are cell-autonomously required to prevent apoptosis in mesencephalic dopaminergic neurons, Alberi L, et al. (2004), Simon HH, et al. (2004). It is especially important to note that En-1 expression and survival effects on dopaminergic neurons of the substantia nigra (SN) and ventral tegmental area (VTA) persist in adults, Sonnier L, et al. (2007) and are neural activity dependent, Di Nardo AA, et al. (2007). The loss of En-1 is linked to apoptosis of midbrain dopaminergic neurons, a condition of Parkinson’s disease. EN-1 is coexpressed with Pax2 within a population of spinal cord ventral interneurons that are directed by Pax6, Burrill JD, et al. (1997), but it is not required for the early specification of ventral interneuron cell types in the embryonic spinal cord, Saueressig H, et al. (1999). En-1 has been identified as a regulator of pathfinding and fasciculation during axon growth, Saueressig H, et al. (1999). En1 expressing spinal interneurons represent a heterogeneous population that connects with both motoneurons (primarily GABAergic) and sensory afferents, Wenner P, et al. (2000). En1 along with Pax6 have essential roles in establishing recurrent inhibitory circuits between motoneurons and Renshaw cells, Sapir T, et al. (2004). Renshaw cells, the interneuronal cell type that mediates recurrent inhibition of motor neurons, are derived from a subset of spinal V1 interneurons. Engrailed-1 is expressed in embryonic ventral limb ectoderm and is essential for dorsal-ventral and proximal-distal limb patterning, Loomis, et al. (1996) and for the proper formation of the apical ectodermal ridge (AER). En1 plays a role in the compaction of the AER into a narrow rim at the tip of the limb, Loomis CA, et al. (1998). En1 is involved in the coordination of AER formation, wherein it is required for positioning and maintenance of two lineage borders, Kimmel RA, et al. (2000); one border is transient and corresponds to the D/V midline of the AER, and the second border corresponds to the dorsal AER margin. Sigma offers antibodies and shRNAs useful for the study of EN1 gene products. References: Ahmed MU, et al. (2006) Establishment of the epaxial-hypaxial boundary in the avian myotome. Dev Dyn. 235: 1884-1894. |
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