Disease relevance of Neurog1

• 2. In the present work, we investigated a instructive potential of Ngn1 in pluripotent embryonal carcinoma P19 cells [1].

High impact information on Neurog1

• We found that Ngn function is required to maintain these two separate expression domains, as Mash1 expression is up-regulated in the dorsal telencephalon of Ngn mutant embryos [2].
• Neurogenin1 (Ngn1), Neurogenin2 (Ngn2), and Mash1 encode bHLH transcription factors with neuronal determination functions [2].
• These findings indicate that SOCS2 promotes neuronal differentiation by blocking growth hormone-mediated downregulation of Ngn1 [3].
• Crossinhibitory activities of Ngn1 and Math1 allow specification of distinct dorsal interneurons [4].
• In vivo and in vitro analyses revealed that mutant neural crest cells emigrate but fail to generate an early wave of sensory neurogenesis that is normally marked by the transcription factor neurogenin (ngn) 2 [5].

Biological context of Neurog1

• Ngn1 and Ngn2 are required to specify the cortical (regional), glutamatergic (neurotransmitter) and laminar (temporal) characters of early-born (lower-layer) neurons, while simultaneously repressing an alternative subcortical, GABAergic neuronal phenotype [6].
• Hair cells in Neurog 1 null mice show cell cycle exit in an apex-to-base progression about 1-2 days earlier [7].
• Neurog 1 null mice show a truncation of clonal expansion of hair cell precursors through temporally altered terminal mitosis, thereby resulting in smaller sensory epithelia [7].
• Thus, the regulatory elements of ngn1 appear to be conserved among vertebrates, with certain differences being incorporated in the utilisation of these enhancers, for the acquisition of more advanced features in amniotes [8].
• The upstream regions of the zebrafish and mammalian ngn1 loci harbour several stretches of conserved sequences [8].

Anatomical context of Neurog1

• Neurogenin (Ngn) 1 and Ngn2 encode basic-helix-loop-helix transcription factors expressed in the developing neocortex [9].
• We propose that the absence of NEUROG 1 protein leads to loss of sensory neuron formation through a phenotypic switch of cycling neurosensory precursors from sensory neuron to hair cell fate [7].
• Smaller inner ear sensory epithelia in Neurog 1 null mice are related to earlier hair cell cycle exit [7].
• Gsh2 is required for the repression of Ngn1 and specification of dorsal interneuron fate in the spinal cord [10].
• Ngn1 is a basic helix-loop-helix (bHLH) transcription factor expressed in specific regions within the developing brain and spinal cord, sensory ganglia, and olfactory epithelium [11].

Associations of Neurog1 with chemical compounds

• Treatment with retinoic acid (RA) induced expression of Ngn1 as well as NeuroD in P19 cells in early period of neuronal differentiation [1].

Regulatory relationships of Neurog1

• Semiquantitative reverse transcriptase-polymerase chain reaction using cranial explants in organ cultures showed that sonic hedgehog (Shh) promotes ngn-1 expression [12].
• We have examined the effects of signaling molecules and Notch signaling on the mechanisms regulating neurogenin (ngn)-2 expression [13].
• Mash1 and Ngn1 control distinct steps of determination and differentiation in the olfactory sensory neuron lineage [14].
• Furthermore, the beta-catenin/TCF complex appears to directly regulate the promoter of neurogenin 1, a gene implicated in cortical neuronal differentiation [15].

Other interactions of Neurog1

• The neurogenesis defect in ngn2(-/-) embryos is transient and later compensated by ngn1-dependent precursors, suggesting that feedback or competitive interactions between these precursors may control the proportion of different neuronal subtypes they normally produce [16].
• We also report that growth hormone inhibited Ngn1 expression and neuronal production, and this action was blocked by SOCS2 overexpression [3].
• We investigated whether co-expression of Neurog 1 and Atoh 1 in common neurosensory precursors could explain the loss of hair cells in Neurog 1 null mice [7].
• Lhx2-/- embryos have, however, a normal distribution of Mash1-positive and neurogenin 1-positive neuronal progenitors that leave the cell cycle, acquire pan-neuronal traits and form axon bundles [17].
• We define restricted neural progenitor populations by the discrete, nonoverlapping expression of Ngn1, Math1, and Mash1 [4].

Analytical, diagnostic and therapeutic context of Neurog1

• In the CNS in situ hybridization to serial sections and double-labeling experiments indicate that Mash1 and ngn1 are expressed in adjacent and nonoverlapping regions of the neuroepithelium that correspond to future functionally distinct areas of the brain [18].
• We show that ventral neural stem cells transfected with Ngn1 are integrated as GABAergic neurons within a few days of transplantation into the adult mouse neocortex [19].

References