PDF(Pubmed)
Abstract：
How our brain generates diverse neuron types that assemble into precise neural circuits remains unclear. Using Drosophila lamina neuron types (L1-L5), we show that the primary homeodomain transcription factor (HDTF) brain-specific homeobox (Bsh) is initiated in progenitors and maintained in L4/L5 neurons to adulthood. Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates while repressing the HDTF Zfh1 to prevent ectopic L1/L3 fates (control: L1-L5; Bsh-knockdown: L1-L3), thereby generating lamina neuronal diversity for normal visual sensitivity. Subsequently, in L4 neurons, Bsh and Ap function in a feed-forward loop to activate the synapse recognition molecule DIP-β, thereby bridging neuronal fate decision to synaptic connectivity. Expression of a Bsh:Dam, specifically in L4, reveals Bsh binding to the DIP-β locus and additional candidate L4 functional identity genes. We propose that HDTFs function hierarchically to coordinate neuronal molecular identity, circuit formation, and function. Hierarchical HDTFs may represent a conserved mechanism for linking neuronal diversity to circuit assembly and function.
摘要：
我们的大脑如何产生不同类型的神经元并组装成精确的神经回路尚不清楚。使用果蝇层神经元类型（L1-L5），我们表明，初级同源结构域转录因子（HDTF）脑特异性同源盒（Bsh）在祖细胞中启动，并在L4/L5神经元中维持到成年。Bsh激活次级HDTFAp（L4）和Pdm3（L5）并指定L4/L5神经元命运，同时抑制HDTFZfh1以防止异位L1/L3命运（对照：L1-L5；Bsh敲除：L1-L3），从而产生正常视觉敏感性的椎板神经元多样性。随后，在L4神经元中，Bsh和Ap在前馈回路中起作用，以激活突触识别分子DIP-β，从而桥接神经元命运决定与突触连接。Bsh的表达式：大坝，特别是在L4中，揭示了Bsh与DIP-β基因座和其他候选L4功能同一性基因的结合。我们建议HDTF分层功能来协调神经元分子同一性，电路形成，和功能。分层HDTF可以代表用于将神经元多样性链接到电路组装和功能的保守机制。
