Asmar Joëlle, Biryukova Inna, Heitzler Pascal
Department of Developmental Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 67404 Illkirch, France.
Dev Biol. 2008 Apr 15;316(2):487-97. doi: 10.1016/j.ydbio.2008.01.040. Epub 2008 Feb 13.
The Drosophila bHLH proneural factors Achaete (Ac) and Scute (Sc) are expressed in clusters of cells (proneural clusters), providing the cells with the potential to develop a neural fate. Mediodorsal proneural patterning is mediated through the GATA transcription factor Pannier (Pnr) that activates ac/sc directly through binding to the dorsocentral (DC) enhancer of ac/sc. Besides, the Gfi transcription factor Senseless (Sens), a target of Ac/Sc, synergizes with ac/sc in the presumptive sensory organ precursors (SOPs). Here we investigate, through new genetic tools, the function of dLMO, the Drosophila LIM only transcription factor that was already known to control wing development. We show that dLMO gene encodes two isoforms, dLMO-RA and dLMO-RB. dLMO null and dLMO-RA(-) deletions have similar phenotypes, lacking thoracic and wing margin sensory organs (SO), while dLMO-RB(-) deletion has normal SOs. At early stages, dLMO-RA is expressed in proneural clusters, however later it is excluded from the SOPs. We found that dLMO functions as a Pnr coactivator to promote ac/sc expression. In the late SOPs, where dLMO-PA is not expressed, Pnr participates to the Sens-dependent regulation of ac/sc. Taken together these results suggest that dLMO-PA is the major isoform that is required for early activation of ac/sc expression.
果蝇bHLH原神经因子achaete(Ac)和scute(Sc)在细胞簇(原神经簇)中表达,赋予细胞发育为神经命运的潜能。中背原神经模式形成是通过GATA转录因子Pannier(Pnr)介导的,Pnr通过与Ac/Sc的背中央(DC)增强子结合直接激活Ac/Sc。此外,Ac/Sc的靶标、Gfi转录因子Senseless(Sens)在假定的感觉器官前体细胞(SOPs)中与Ac/Sc协同作用。在这里,我们通过新的遗传工具研究了dLMO的功能,dLMO是果蝇中已知控制翅膀发育的仅含LIM结构域的转录因子。我们发现dLMO基因编码两种异构体,dLMO-RA和dLMO-RB。dLMO基因敲除和dLMO-RA(-)缺失具有相似的表型,缺乏胸部和翅缘感觉器官(SO),而dLMO-RB(-)缺失的SO正常。在早期阶段,dLMO-RA在原神经簇中表达,但后来被排除在SOPs之外。我们发现dLMO作为Pnr的共激活因子来促进Ac/Sc的表达。在晚期SOPs中,dLMO-PA不表达时,Pnr参与Ac/Sc的Sens依赖性调控。综合这些结果表明,dLMO-PA是Ac/Sc表达早期激活所需的主要异构体。