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Transcription factors in neurogenesis


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Transcription factors in neurogenesis

Transcription factors in neurogenesis

On the molecular level, early development of the vertebrate nervous system is similarand occurs in parallel to that of other embryonic tissues. The molecules involved aresimilar to those of the tissues as diverse as lung, muscle and bone. Formation of thecentral nervous system involves neural induction, maturation, and specification. Numerousintracellular transcription factors are involved at each stage [1]. Adultneurogenesis has been found in all mammals. The process of adult neurogenesis encompassesthe proliferation of resident neural stem and progenitor cells and their subsequentdifferentiation, migration, and functional integration into the pre-existing circuitry[2]. Described here are some of the transcription factors involved in theregulation of these processes.

SRY (sex determining region Y)-box proteins ( SOX ) are activated at very earlyand later stages of the central nervous system development, maturation and induction.Achaete-scute complex homolog 1 ( hASH1 ) and Hairy and enhancer of split 1 (HES1 ) are activated during maturation [1]. Neurogenin andhASH1 are known to determine fates of the glutamatergic versus the GABAergic cellsin the forebrain and spinal cord neurons [3]. HES (for example HES1 )functions as transcriptional repressors and is an essential effector of theNotch-mediated inhibition of neuronal differentiation in development. HES1maintains neural progenitor cells in the undifferentiated and proliferative state [4]. SOX3 participates in induction of cell proliferation [1].Transcription factors of the POU class ( POU ) are activated later and participatein specification of neuronal cell subsets in brain [1]. POUs regulate thetranscription of diverse genes in central nervous system stem cells and regulate stemcells state.[5]. Orthodenticle homeobox ( OTX ) and Distal-lesshomeobox ( Dlx ) are activated early and participate in antero-posteriorspecification in the brain. Paired box ( Pax ) is activated early and participatesin dorso-ventral specification in neural tube [1]. Myocyte enhancer factor 2C( MEF2C ) plays role in programming of the early differentiation and properdistribution of the neurons within the layers of the neocortex [6].Neurogenins and their downstream target Neurogenic differentiation ( NeuroD )protein are able to direct the development of multipotent precursors of the nerve andectodermal cells, and even muscle precursors, into differentiated neurons. Atonal homolog1 ( ATH1 ) and Neurogenin s can serve as vertebrate neuronal determinationgenes. Zic family members ( Zics ) can inhibit neuronal differentiation byactivating Notch signals [7]. ASCL1 achaete-scute complex homolog 1 (Mash-1 ) participates in the initial step of differentiation of the stem cells[8]. Nescient helix loop helix 1 and 2 ( HEN1 and NHLH2 )control expression of Necdin. The latter induces neuronal cell differentiationand inhibits cell proliferation [9]. Hairy/enhancer-of-split related withYRPW motif 1 and 2 ( HEY1 and HEY2 ) inhibit transcription induced by theATH1 and thus promote maintenance of neural precursor cell state [10].GAP43 growth associated protein 43 ( Neuromodulin ) is expressed in proliferatingneuroblasts and is required for maturation of neurons [11].