Zebrafish dorsal root ganglia neural precursor cells adopt a glial fate in the absence of neurogenin1.
The proneural transcription factor neurogenin 1 (neurog1) has been shown to be a key regulator of dorsal root ganglion (DRG) neuron development. Here we use a novel transgenic zebrafish line to demonstrate that the neural crest population that gives rise to DRG neurons becomes fate restricted to a neuronal/glial precursor before the onset of neurog1 function. We generated a stable transgenic zebrafish line that carries a modified bacterial artificial chromosome that expresses green fluorescent protein (GFP) under the control of the neurog1 promoter [Tg(neurog1:EGFP)]. In contrast to previously described neurog1 transgenic lines, Tg(neurog1:EGFP) expresses GFP in DRG neuronal precursors cells as they migrate ventrally and after their initial differentiation as neurons. Using this line, we are able to track the fate of DRG neuronal precursor cells during their specification. When Neurog1 function is blocked, either by neurog1 morpholino antisense oligonucleotide injection or in neurog1 mutants, GFP expression initiates in neural crest cells, although they fail to form DRG neurons. Rather, these cells take on a glial-like morphology, retain proliferative capacity, and express glial markers and become associated with the ventral motor root. These results suggest that, within the zebrafish neural crest, there is a fate-restricted lineage that is limited to form either sensory neurons or glia in the developing DRG. Neurog1 acts as the key factor in this lineage to direct the formation of sensory neurons.
McGraw
Hillary F
HF
Molecular and Cellular Biology Program and Department of Biological Structure, University of Washington, Seattle, Washington 98195, USA.
Nechiporuk
Alexei
A
Raible
David W
DW
D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency* / Q000235:genetics; D019521:Body Patterning / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D004625:Embryo, Nonmammalian; D005727:Ganglia, Spinal / Q000166:cytology* / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D009025:Morpholines / Q000494:pharmacology; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D055757:SOXE Transcription Factors / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014704:Veratrum Alkaloids / Q000494:pharmacology; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D009025:Morpholines; D009419:Nerve Tissue Proteins; D055757:SOXE Transcription Factors; D014704:Veratrum Alkaloids; D029961:Zebrafish Proteins; C486337:neurog1 protein, zebrafish; C442229:sox10 protein, zebrafish; C037574:morpholine; C000541:cyclopamine