A genome-wide analysis reveals that the Drosophila transcription factor Lola promotes axon growth in part by suppressing expression of the actin nucleation factor Spire.
A genome-wide analysis reveals that the Drosophila transcription factor Lola promotes axon growth in part by suppressing expression of the actin nucleation factor Spire.
复制标题
DOI：
10.1186/1749-8104-6-37
复制
发表时间：
2011-11-30
影响因子：
3.6
通讯作者：
Giniger E
中科院分区：
文献类型：
--
作者：
Gates MA;Kannan R;Giniger E
系统发育上保守的转录因子 Lola 对于果蝇轴突生长和引导、突触形成和神经回路发育的许多方面至关重要。然而，迄今为止，很难全面了解 Lola 的功能和机制。我们使用表达微阵列来鉴定果蝇胚胎中的 lola 依赖性转录组。我们发现 lola 调节大量基因的表达，这些基因已知会影响几种 lola 依赖性发育过程。在其他基因座中，我们发现 lola 是 spire 的负调节因子，这是一种肌动蛋白成核因子，已因其在卵子发生中的重要作用而被研究。我们证明尖顶在神经系统中表达，并且是已知的 Lola 依赖性轴突引导决策（ISNb 运动轴突生长）所必需的。我们进一步表明，减少 spire 基因剂量会抑制 lola 表型的这一方面，验证 spire 的去抑制是 lola 突变体中胚胎运动轴突轴突停滞表型的重要贡献者。这些数据为许多 Lola 依赖性过程的分子机制提供了新的线索，并且还确定了一些先前与 Lola 无关但易于受该转录因子调节的发育过程。这些数据进一步证明，肌动蛋白成核因子 Spire 的过度表达与 Spire 的丢失一样对体内轴突生长有害，因此强调需要在肌动蛋白动力学的基本步骤中保持平衡，以实现有效的神经元形态发生。
The phylogenetically conserved transcription factor Lola is essential for many aspects of axon growth and guidance, synapse formation and neural circuit development in Drosophila. To date it has been difficult, however, to obtain an overall view of Lola functions and mechanisms. We use expression microarrays to identify the lola-dependent transcriptome in the Drosophila embryo. We find that lola regulates the expression of a large selection of genes that are known to affect each of several lola-dependent developmental processes. Among other loci, we find lola to be a negative regulator of spire, an actin nucleation factor that has been studied for its essential role in oogenesis. We show that spire is expressed in the nervous system and is required for a known lola-dependent axon guidance decision, growth of ISNb motor axons. We further show that reducing spire gene dosage suppresses this aspect of the lola phenotype, verifying that derepression of spire is an important contributor to the axon stalling phenotype of embryonic motor axons in lola mutants. These data shed new light on the molecular mechanisms of many lola-dependent processes, and also identify several developmental processes not previously linked to lola that are apt to be regulated by this transcription factor. These data further demonstrate that excessive expression of the actin nucleation factor Spire is as deleterious for axon growth in vivo as is the loss of Spire, thus highlighting the need for a balance in the elementary steps of actin dynamics to achieve effective neuronal morphogenesis.
登录
查看更多内容
影响因子：
10.5
作者：
LUO, LQ;LIAO, YJ;JAN, YN
通讯作者：
JAN, YN
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
2.7
作者：
Bass, B. Paige;Cullen, Kristen;McCall, Kimberly
通讯作者：
McCall, Kimberly
影响因子：
2.7
作者：
Madden, K;Crowner, D;Giniger, E
通讯作者：
Giniger, E
影响因子：
64.5
作者：
GHYSEN, A;JAN, LY;JAN, YN
通讯作者：
JAN, YN