Neurogenin 1 (Neurog1) expression in the ventral neural tube is mediated by a distinct enhancer and preferentially marks ventral interneuron lineages.
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 0.8 kb 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.
Quiñones
Herson I
HI
Department of Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9111, USA.
Savage
Trisha K
TK
Battiste
James
J
Johnson
Jane E
JE
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D019070:Cell Lineage; D022202:Chromosomes, Artificial, Bacterial; D004622:Embryo, Mammalian; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008845:Microinjections; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D054259:Neural Tube / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology; D019076:Transgenes / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D009419:Nerve Tissue Proteins; C486336:Neurog1 protein, mouse