RGD Reference Report - Contrasting and brain region-specific roles of neurogenin2 and mash1 in GABAergic neuron differentiation in vitro. - Rat Genome Database

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Contrasting and brain region-specific roles of neurogenin2 and mash1 in GABAergic neuron differentiation in vitro.

Authors: Jo, AY  Park, CH  Aizawa, S  Lee, SH 
Citation: Jo AY, etal., Exp Cell Res. 2007 Nov 15;313(19):4066-81. Epub 2007 Sep 8.
RGD ID: 2314144
Pubmed: PMID:17936272   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yexcr.2007.08.026   (Journal Full-text)

We have cultivated highly uniform populations of neural precursor cells, which retain their region-specific identities, from various rat embryonic brain regions. The roles of the proneural basic-helix-loop-helix (bHLH) factors neurogenin2 (Ngn2) and Mash1 in gamma-aminobutyric acid (GABA) neuron differentiation were explored in the region-specific cultures. Consistent with previous in vivo studies, forced expression of Mash1 promoted GABA neuron formation from the precursors derived from the developing forebrains, whereas Ngn2 displayed an inhibitory role in forebrain GABA neuron differentiation. Functional analyses of mutant bHLH proteins indicated that the helix-loop-helix domains of Mash1 and Ngn2, known as the structures for protein-protein interactions, impart the distinct activities. Intriguingly, the regulatory activities of Mash1 and Ngn2 in GABA neuron differentiation from the hindbrain- and spinal cord-derived precursor cells were completely opposite of those observed in the forebrain-derived cultures: increased GABA neuron yield by Ngn2 and decreased yield by Mash1 were shown in the precursors of those posterior brain regions. No clear difference that depended on dorsal-ventral brain regions was observed in the bHLH-mediated activities. Finally, we demonstrated that Otx2, the expression of which is developmentally confined to the regions anterior to the isthmus, is a factor responsible for the anterior-posterior region-dependent opposite effects of the bHLH proteins.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ascl1Ratforebrain neuron differentiation  IDA  RGD 
Ascl1Ratnegative regulation of neuron differentiation  IDA  RGD 
Ascl1Ratpositive regulation of neuron differentiation  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ascl1  (achaete-scute family bHLH transcription factor 1)


Additional Information