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Achaete-scute complex-like 1 (Drosophila) (Gene ASCL1) Homo sapiensThe ASCL1 (map locus: Entrez/HGNC 12q22-q23; Ensembl 12q23.2) gene, MASH1/achaete-scute homolog 1, is a 236 AA (25.4 kDa) basic helix-loop-helix (bHLH) transcription factor with a 40 AA helix-loop-helix motif (132 to 171) and a HLH N-terminal adjacent DNA-binding 11 AA basic motif (121-131). The protein also contains closely linked 15 AA polyAla (33-47) and 12 AA polyGln (51-62) regions. BasicHLH transcription factors are heterodimeric. Mash1 is essential for neuronal differentiation and specification within the nervous system. MASH1 (ASCL1) is expressed in temporally and spatially restricted domains of the neuroepithelium of developing CNS and PNS where it helps determine regionalization of the future brain and spinal cord. Mash1 and ngn1 are expressed in adjacent, non-overlapping regions of the neuroepithelium, Ma Q, et al. (1997) and Mash1 and ngn2 are expressed in complementary populations of the CNS and PNS, Parras CM. et al. (2002). Ngn2 and Mash1 function together to regulate the zonal distribution of progenitors in the developing neocortex, Britz O, et al. (2006). Mash1 progenitor cells at early stages in each CNS region preferentially become neurons, and at late stages they become oligodendrocytes, Kim EJ, et al. (2008). Mash1 is required for neurogenesis in the ventral telencephalon and specific areas of the diencephalon, Horton S, et al. (1999), Casarosa S, et al. (1999), Yun K and Fischman S, et al. (2002). Neural crest cells (NCC) are a migratory population that differentiates into neurons and glia of the peripheral nervous system (the autonomic system) and various non-neural mesectodermal and endocrine cells types. Mash1 plays a variety of roles in the development and speciation of NCC cell progeny, Lo LC, et al. (1991). Mash1 and Phox2b are essential for NCC neuron development into sympathetic, parasympathetic, and enteric ganglia components of the peripheral autonomic nervous system, Pattyn A, et al. (1999). MASH1 is expressed (BMP2-induced) initially in the neural committed non-neural precursor cells of the autonomic nervous system, Anderson DJ (1994), Sommer L, et al. (1995), Anderson DJ, (1997). These MASH1+ precursor cells differentiate further into sympathetic, parasympathetic and enteric neuron subtypes. Mash1 is involved in the development of a variety of cell types throughout the CNS and PNS. In the forebrain neocortex, Mash1 promotes the differentiation of GABAergic local circuit neurons. Mash1+ progenitor cells located in the neocortical ventricular and subventricular zone of the dorsal forebrain differentiate into a GABAergic lineage (also Dlx1/2 positive) that represents 65% of the neocortical GABAergic neurons in humans, Letinic K, et al. (2002). Conversely, Mash1 suppresses GABAergic neurons in the hindbrain and spinal cord, Jo AY, et al. (2007). Mash1 is expressed in a subset of oligodendrocyte precursors (OPCs) as soon as they are generated in the forebrain ventricular zone and it cooperates with Olig2 in OPC specification, Parras CM, et al. (2007). Mash1 supports the division of neural progenitor cells (NPC) from the ventral midbrain (VM) while maintaining neurogenic potential. In cooperation with Nurr1, Mash1 contributes to the generation of dopaminergic (DA) neurons, Park CH, et al. (2006), Kim HJ, et al. (2007). Mash1 function is essential for the development of all central and peripheral neurons that express noradrenergic traits transiently or permanently, Hirsh MR, et al. (1998). In the hindbrain, Mash1 and Math3 promote branchiomotor neuron development and regulate subsequent oligodendrocyte development, Ohsawa R, et al. (2005). Mash1 is coexpressed with Nkx2-2 in the neuroepithelial domain of the hindbrain, which gives rise to 5-HT neurons. Mash1 is essential for the development of 5-HT neurons (serotonergic) as a proneural gene for the production of postmitotic neuronal precursors and as a determinant of the serotonergic phenotype, Pattyn A, et al. (2004). Mash1 supports the differentiation of specific cell subpopulation within the spinal cord. The ventral spinal cord p2 progenitor domain gives rise to interneurons V2a and V2b. Mash1 acts synergistically with Foxn4 to specify the development of V2b interneurons, Li S, et al. (2005), Del Barrio MG, et al. (2007). The major neuronal subtypes in the dorsal spinal cord are dILA and dILB neurons. A Mash1+ progenitor population gives rise to the dILA and dILB neurons of the dorsal spinal cord; however, Mash1 promotes the final differentiation of dILA, but not dILB, Wildner H, et al. (2006). Mash 1 supports the differentiation of several neuroendocrine cell types including chromaffin cells that are derived from neural crest derived sympathoadrenal (SA) progenitors, Huber K, et al. (2002), Unsicker K, et al. (2005); hypothalamic propiomelanocortin (POMC+) neurons, McNay DE, et al. (2006) and gastric neuroendocrine cells, Kokubu H, et al. (2008). Mash1 is required for the development of a variety of other cell types including chemoreceptive glomus cells of the carotid body, Kameda Y. (2005), olfactory neurons, Cau E, et al. (1997, 2002), basal cells and type II cells of taste buds, Seta Y, et al. (2006), Miura H, et al. (2006), and C-cells of the thyroid gland, Kameda Y, et al. (2007). Studies of the expression profiles, genetic cascades and regulatory roles of Mash1 may enhance an understanding or treatment of several major medical conditions. A recent study has suggested that Mash1 may be useful in the development of motoneurons to treat spinal cord injuries, Hamada M, et al. (2006). Mash1 is involved in a beta-Amyloid (Abeta) induced process that promotes cell death, Uchida Y, et al. (2007) associated with Alzheimer’s disease. Since Mash1 is involved in the development of dopaminergic neurons, it may be important to scientists for understanding and treatment of Parkinson’s disease. Mash1 has been identified as a positive adjunct marker of pulmonary small cell carcinoma versus Merkel cell carcinoma, Ralston J, et al. (2008). Sigma offers antibodies and shRNAs useful for the study of ASCL1 (MASH1) gene products. References: Anderson DJ, et al. (1997) Cell lineage determination and the control of neuronal identity in the neural crest. Cold Spring Harb Symp Quant Biol. 62: 493-504. |
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