演題番号 : P1-d23
大迫 俊二 / Shunji Ohsako:1 山田 隆文 / Takafumi Yamada:1
1:東京都神経科学総合研究所 / Tokyo Metropolitan Institute for Neuroscience
Neural zinc finger factor (NZF)/myelin transcription factor (MyT) gene family is constituted of transcription factors with DNA-binding domains of a Cys-X5-Cys-X12-His-X4-Cys (C2HC)-type Zn finger conserved from C. elegans to human. Xenopus MyT1 (also designated as NZF-2) was shown to play a critical role in neuronal differentiation, although human MyT1 was first identified by virtue of its binding to cis-regulatory elements of a glia-specific gene, the myelin proteolipid protein gene. On the other hand, NZF-1 (also designated as MyT1l or Png-1) was shown to be expressed in postmitotic neurons. The functions of the NZF/MyTgene family, however, remain elusive. To clarify NZF/MyT functions, we previously identified a Drosophila homolog dNZF. Although only one cDNA clone was isolated, RT-PCR analysis showed that multiple transcripts are generated by alternative splicing of the dnzf gene. Immunoblot analysis partially confirmed the presence of the isoforms. dnzf mutants that almost die at the pharate adult stage, were generated by imprecise excision of a P-element transposon inserted near the transcriptional start site of the dnzf gene. A few adult escapers, however, showed an uncoordinated movement, and died shortly thereafter. Immunohistochemical analysis showed that dNZF is expressed in subsets of neurons from embryo to adult. We generated dnzf-GAL4 line that mimics the endogenous expression pattern using targeted transposition. Blockage of neural transmission in adult flies by dnzf-GAL4 driven temperature-sensitive dynamin (shibire) expression at the non-permissive temperature, caused an uncoordinated movement as seen in dnzf mutant escapers. Expression of a dominant-negative form of dNZF by dnzf-GAL4 also caused adult pharate lethality and aberrant synaptic terminal formation. These results suggest that that the dnzf gene may be required in differentiation of neuronal subsets.