title: Distinct cis regulatory elements govern the expression of TAG1 in embryonic sensory ganglia and spinal cord.
abstract: Cell fate commitment of spinal progenitor neurons is initiated by long-range, midline-derived, morphogens that regulate an array of transcription factors that, in turn, act sequentially or in parallel to control neuronal differentiation. Included among these are transcription factors that regulate the expression of receptors for guidance cues, thereby determining axonal trajectories. The Ig/FNIII superfamily molecules TAG1/Axonin1/CNTN2 (TAG1) and Neurofascin (Nfasc) are co-expressed in numerous neuronal cell types in the CNS and PNS - for example motor, DRG and interneurons - both promote neurite outgrowth and both are required for the architecture and function of nodes of Ranvier. The genes encoding TAG1 and Nfasc are adjacent in the genome, an arrangement which is evolutionarily conserved. To study the transcriptional network that governs TAG1 and Nfasc expression in spinal motor and commissural neurons, we set out to identify cis elements that regulate their expression. Two evolutionarily conserved DNA modules, one located between the Nfasc and TAG1 genes and the second directly 5' to the first exon and encompassing the first intron of TAG1, were identified that direct complementary expression to the CNS and PNS, respectively, of the embryonic hindbrain and spinal cord. Sequential deletions and point mutations of the CNS enhancer element revealed a 130bp element containing three conserved E-boxes required for motor neuron expression. In combination, these two elements appear to recapitulate a major part of the pattern of TAG1 expression in the embryonic nervous system.
authors.affiliation: Dept. of medical neurobiology, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Hadas
authors.forename: Noa
authors.initials: N
authors.lastname: Nitzan
authors.forename: Andrew J W
authors.initials: AJ
authors.lastname: Furley
authors.forename: Serguei V
authors.initials: SV
authors.lastname: Kozlov
authors.forename: Avihu
authors.initials: A
authors.lastname: Klar
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002642:Chick Embryo; D017124:Conserved Sequence; D058969:Contactin 2 / Q000235:genetics*; D024721:E-Box Elements / Q000235:genetics; D019143:Evolution, Molecular; D017950:Ganglia, Sensory / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000378:metabolism; D016296:Mutagenesis; D009414:Nerve Growth Factors / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012249:Rhombencephalon / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015815:Cell Adhesion Molecules; D058969:Contactin 2; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse