Helt determines GABAergic over glutamatergic neuronal fate by repressing Ngn genes in the developing mesencephalon

• DOI: 10.1242/dev.02870
• Publication Date: 2007-07-05T02:12:00Z
• Authors: Tomoya Nakatani; Yasuko Minaki; Minoru Kumai; Yuichi Ono
• Keywords: Mice, Knockout; Neurons; 0301 basic medicine; 0303 health sciences; Stem Cells; Down-Regulation; Gene Expression Regulation, Developmental; Glutamic Acid; Cell Differentiation; Nerve Tissue Proteins; Models, Biological; Mice, Inbred C57BL; Repressor Proteins; Mice; 03 medical and health sciences; Homeobox Protein Nkx-2.2; Mesencephalon; Organ Specificity; Basic Helix-Loop-Helix Transcription Factors; Animals; gamma-Aminobutyric Acid

The mechanism underlying the determination of neurotransmitter phenotype in developing mesencephalon, particularly GABAergic versus glutamatergic fate, remains largely unknown. Here, we show mice that basic helix-loop-helix transcriptional repressor gene Helt (also known as Megane and Heslike) functions a selector determines over fate mesencephalon. was coincidently expressed all progenitor domains for mesencephalic neurons. In mesencephalon Helt-deficient embryos, neurons were mostly absent emerged instead. Conversely, ectopically suppressed formation induced neurogenesis. However, mutants showed normal domain formation. consequence, postmitotic expression homeodomain factor Nkx2.2, which specifically by populations wild-type maintained despite transmitter conversion from to mutants, suggesting is not involved neuronal identity specification. Furthermore, identified proneural genes Ngn1 Ngn2, selectively progenitors had ability confer downstream target Helt. These results suggest at least part, repressing Ngn (Neurog) transcription networks involving Ngns are commonly used phenotype.