4 research outputs found
Distinct Cis Regulatory Elements Govern the Expression of TAG1 in Embryonic Sensory Ganglia and Spinal Cord
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 59 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