Neurogenin 1 (Neurog1) expression in the ventral neural tube is mediated by a distinct enhancer and preferentially marks ventral interneuron lineages

• Published in: Developmental biology Vol. 340; no. 2; pp. 283 - 292
• Main Authors: Quiñones, Herson I., Savage, Trisha K., Battiste, James, Johnson, Jane E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.04.2010
• Subjects: Animal models; Animals; BAC transgenic mice; Base Sequence; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - metabolism; bHLH transcription factor; Cell Lineage; Chromosomes, Artificial, Bacterial; Cre recombinase; Embryo, Mammalian; Enhancer Elements, Genetic; Gene Expression Regulation, Developmental; Gene regulation; Green Fluorescent Proteins - metabolism; Immunohistochemistry; Interneurons - cytology; Interneurons - physiology; Mice; Mice, Transgenic; Microinjections; Molecular Sequence Data; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neural Tube - cytology; Neural Tube - embryology; Neural Tube - physiology; Neural tube enhancer; Neurogenesis; Neurogenin; Ngn1; Spinal cord development; Stem Cells - cytology; Transgenes - genetics; Ventral spinal cord interneurons; BAC transgenic mice; Spinal cord development; bHLH transcription factor; Gene regulation; Ngn1; Neurogenesis; Neural tube enhancer; Cre recombinase; Neurogenin; Ventral spinal cord interneurons
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2010.02.012

The bHLH transcription factor Neurog1 (Ngn1, Neurod3, neurogenin 1) is involved in neuronal differentiation and cell-type specification in distinct regions of the developing nervous system. Here, transgenic mouse models were developed that use a Bacterial Artificial Chromosome (BAC) containing 208kb flanking the Neurog1 gene to efficiently drive expression of GFP and Cre in all Neurog1 domains. Two characteristics of Neurog1 gene regulation were uncovered. First, a 4kb region previously shown to be sufficient for driving expression of a reporter gene to a subset of the Neurog1 pattern in the developing midbrain, hindbrain, and spinal cord is required uniformly for high levels of expression in all Neurog1 domains, even those not originally identified as being regulated by this region. Second, a 0.8kb enhancer was identified that is sufficient to drive Neurog1-like expression specifically in the ventral neural tube. Furthermore, Neurog1 progenitor cells in the ventral neural tube are largely fated to interneuron lineages rather than to motoneurons. These studies provide new tools for directing tissue specific expression in the developing neural tube, define Neurog1 lineages in the spinal cord, and further define the complex genomic structure required for obtaining the correct levels and spatial restriction of the neuronal differentiation gene Neurog1.