Proximal-distal leg development in Drosophila requires the apterous gene and the Lim1 homologue dlim1

Proximal-distal leg development in Drosophila involves a battery of genes expressed and required in specific proximal-distal (PD) domains of the appendage. Here we report the characterisation of a new gene of this type, dlim1, a member of the Lhx family of genes whose proteins contain two Lim domains and a homeodomain. We show that the Lhx gene apterous (ap) is also required for PD leg development, and we study the functional interactions between ap, dlim1 and other PD genes during leg development. Our results show that a regulatory network formed by ap and dlim1 plus the homeobox genes aristaless and Bar specifies distal leg cell fates in Drosophila.     

LIM同源框基因家族与神经系统

同源框基因是指一类含有同源序列的基因,它编码的蛋白质作为转录调节因子调节细胞的发育和分化,控制基因的表达形式。ＬＩＭ同源框基因不仅含有同源框基因也含有编码ＬＩＭ结构域的保守序列。     

even-skipped determines the dorsal growth of motor axons in Drosophila

Axon pathfinding and target choice are governed by cell type-specific responses to external cues. Here, we show that in the Drosophila embryo, motorneurons with targets in the dorsal muscle field express the homeobox gene even-skipped and that this expression is necessary and sufficient to direct motor axons into the dorsal muscle field. Previously, it was shown that motorneurons projecting to ventral targets express the LIM homeobox gene islet, which is sufficient to direct axons to the ventral muscle field. Thus, even-skipped complements the function of islet, and together these two genes constitute a bimodal switch regulating axonal growth and directing motor axons to ventral or to dorsal regions of the muscle field.     

Characterization of Lhx9, a novel LIM/homeobox gene expressed by the pioneer neurons in the mouse cerebral cortex.

In order to explain the phenotype observed in Lhx2 mutant embryos, we previously proposed that an Lhx2 related gene might exist. We now have cloned a new LIM/homeobox gene called Lhx9. Lhx9 is closely related to Lhx2 and is expressed in the developing central nervous system (CNS). Lhx9 and Lhx2 have expression patterns that overlap in some areas but are distinct in others. Thus, in some developmental domains these two highly related proteins may be functionally redundant. Lhx9 is expressed in the pioneer neurons of the cerebral cortex, while Lhx2 is expressed throughout the cortical layers. Postnatally, Lhx9 is expressed in the inner nuclei of the cerebellum, while Lhx2 is in the granular layer. In the developing limbs, both genes are highly expressed in a similar pattern. Based on the expression pattern and the developmental regulation of Lhx9, we propose that Lhx9 may be involved in the specification or function of the pioneer neurons of the cerebral cortex. We show that both Lhx9 and Lhx2 bind the LIM domain binding protein Ldb1/Nli1/Clim2.     

The Caenorhabditis elegans lim-6 LIM homeobox gene regulates neurite outgrowth and function of particular GABAergic neurons

We describe here the functional analysis of the C. elegans LIM homeobox gene lim-6, the ortholog of the mammalian Lmx-1a and b genes that regulate limb, CNS, kidney and eye development. lim-6 is expressed in a small number of sensory-, inter- and motorneurons, in epithelial cells of the uterus and in the excretory system. Loss of lim-6 function affects late events in the differentiation of two classes of GABAergic motorneurons which control rhythmic enteric muscle contraction. lim-6 is required to specify the correct axon morphology of these neurons and also regulates expression of glutamic acid decarboxylase, the rate limiting enzyme of GABA synthesis in these neurons. Moreover, lim-6 gene activity and GABA signaling regulate neuroendocrine outputs of the nervous system. In the chemosensory system lim-6 regulates the asymmetric expression of a probable chemosensory receptor. lim-6 is also required in epithelial cells for uterine morphogenesis. We compare the function of lim-6 to those of other LIM homeobox genes in C. elegans and suggest that LIM homeobox genes share the common theme of controlling terminal neural differentiation steps that when disrupted lead to specific neuroanatomical and neural function defects.     

青岛文昌鱼LIM类基因Bblim同源框区的cDNA克隆、序列分析及其在胚胎发育中的表达(英文)

不同卵裂球发育命运的特化、亦即胚胎细胞的分化是动物胚胎发育的重要特征。多数胚胎细胞尽管形态特征完全一致,却具有完全不同的发育命运。预示着：在这些细胞中存在有决定发育命运的因素———决定子。本工作克隆了青岛文昌鱼ＬＩＭ类同源框基因的同源框片段。目的在于揭示决定子的分子本质。青岛近海采集性成熟的成年青岛文昌鱼,收集未受精卵、受精卵以及各个不同时期的胚胎,液氮冻存备用。分别制备总ＲＮＡ。根据其它动物ＬＩＭ类同源框基因的序列设计引物（Ｔａｂ．１）,连续进行ＲＴＰＣＲ和ＰＣＲ两次扩增。其中,原肠胚来源的第二次ＰＣＲ产物经电泳鉴定（Ｆｉｇ．１）后,酶切、克隆入质粒、测序、将该片段所在的基因命名为Ｂｂｌｉｍ基因,该片段称为Ｂｂｌｉｍ同源框。根据Ｂｂｌｉｍ基因同源框的核苷酸序列推导出其相应的氨基酸序列（Ｆｉｇ．２）,与其它ＬＩＭ类同源框基因进行比较（Ｆｉｇ．３）后,认为：Ｂｂｌｉｍ基因可归入ｌｉｍ３类基因。比较胚胎发育各个不同时期第二次ＰＣＲ产物的含量———即Ｂｂｌｉｍ基因的转录（Ｆｉｇ．４）,提示：该基因可能在受·精·后·和·原·肠·形·成·期·前·后·两个发育阶段起作用。此外,Ｂｂｌｉｍ基因的同源域与海鞘Ｈｒｌｉｍ的     

The LIM Class Homeobox Gene lim5: Implied Role in CNS Patterning in Xenopus and Zebrafish

LIM homeobox genes are characterized by encoding proteins in which two cysteine-rich LIM domains are associated with a homeodomain. We report the isolation of a gene, named Xlim-5 in Xenopus and lim5 in the zebrafish, that is highly similar in sequence but quite distinct in expression pattern from the previously described Xlim-1/lim1 gene. In both species studied the lim5 gene is expressed in the entire ectoderm in the early gastrula embryo. The Xlim-5 gene is activated in a cell autonomous manner in ectodermal cells, and this activation is suppressed by the mesoderm inducer activin. During neurulation, expression of the lim5 gene in both the frog and fish embryo is rapidly restricted to an anterior region in the developing neural plate/keel. In the 2-day Xenopus and 24-hr zebrafish embryo, this region becomes more sharply defined, forming a strongly lim5-expressing domain in the diencephalon anterior to the midbrain-forebrain boundary. In addition, regions of less intense lim5 expression are seen in the zebrafish embryo in parts of the telencephalon, in the anterior diencephalon coincident with the postoptic commissure, and in restricted regions of the midbrain, hindbrain, and spinal cord. Expression in ventral forebrain is abolished from the 5-somite stage onward in cyclops mutant fish. These results imply a role for lim5 in the patterning of the nervous system, in particular in the early specification of the diencephalon.     

人同源框基因Lhx4 cDNA序列的获得,染色体定位和基因组分析

Lhx4基因是LIM同源框基因家族的一员 ,它在运动神经元的发育过程中发挥着重要的作用 .从人脊髓cDNA文库中筛选到了 1个人源性Lhx4基因的cDNA全长序列 ,它与鼠源性的Lhx4基因的cDNA序列有 92 %同源性 .它的基因被定位在 1号染色体 1q 2 4 .1- 1q 2 4 .3的位置 ,并包含有 6个外显子 .其中同源框结构域由外显子 4和 5表达 ,LIM结构域 1由外显子 2表达 ,LIM结构域2由外显子 3表达 .     

Apterous is a Drosophila LIM domain gene required for the development of a subset of embryonic muscles.

The recently discovered LIM motif is found in a set of homeodomain-containing proteins thought to mediate the generation of particular cell types. Of the four LIM domain family members described to date, mec-3 and lin-11 determine cell lineages in C. elegans. Isl-1 and Xlim-1 may play similar roles in vertebrates. We have identified a Drosophila member of this class, the product of the apterous (ap) gene. During embryogenesis, ap is expressed in a small subset of fusing mesodermal precursors that give rise to 6 muscles in each abdominal hemisegment and in 5 neurons within each corresponding CNS hemisegment. Lack of ap function results in loss of ap-expressing muscles, while misexpression of ap using a heterologous promoter produces ectopic muscles.     

LIM homeobox gene-dependent expression of biogenic amine receptors in restricted regions of the C. elegans nervous system

Biogenic amines regulate a variety of behaviors. Their functions are predominantly mediated through G-protein-coupled 7-transmembrane domain receptors (GPCR), 16 of which are predicted to exist in the genome sequence of the nematode Caenorhabditis elegans. We describe here the expression pattern of several of these aminergic receptors, including two serotonin receptors (ser-1 and ser-4), one tyramine receptor (ser-2), and two dopamine receptors (dop-1 and dop-2). Moreover, we describe distinct but partially overlapping expression patterns of different splice forms of the ser-2 tyramine receptor locus. We find that each of the aminergic receptor genes is expressed in restricted regions of the nervous system and that many of them reveal significant overlap with the expression of regulatory factors of the LIM homeobox (Lhx) gene family. We demonstrate that the expression of several of the biogenic amine receptors is abrogated in specific cell types in Lhx gene mutants, thus establishing a role for these Lhx genes in regulating aspects of neurotransmission. We extend these findings with other cell fate markers and show that the lim-4 Lhx gene is required for several but not all aspects of RID motor neuron differentiation and that the lim-6 Lhx gene is required for specific aspects of RIS interneuron differentiation. We also use aminergic receptor gfp reporter fusions as tools to visualize the anatomy of specific neurons in Lhx mutant backgrounds and find that the development of the elaborate dendritic branching pattern of the PVD harsh touch sensory neuron requires the mec-3 Lhx gene. Lastly, we analyze a mutant allele of the ser-2 tyramine receptor, a target of the ttx-3 Lhx gene in the AIY interneuron class. ser-2 mutants display none of the defects previously shown to be associated with loss of AIY function.     

Ghox 4.7: a chick homeobox gene expressed primarily in limb buds with limb-type differences in expression.

Homeobox genes play a key role in specifying the segmented body plan of Drosophila, and recent work suggests that at least several homeobox genes may play a regulatory role during vertebrate limb morphogenesis. We have used degenerate oligonucleotide primers from highly conserved domains in the homeobox motif to amplify homeobox gene segments from chick embryo limb bud cDNAs using the polymerase chain reaction. Expression of a large number of homeobox genes (at least 17) is detected using this approach. One of these genes contains a novel homeobox loosely related to the Drosophila Abdominal B class, and was further analyzed by determining its complete coding sequence and evaluating its expression during embryogenesis by in situ hybridization. Based on sequence and expression patterns, we have designated this gene as Ghox 4.7 and believe that it is the chick homologue of the murine Hox 4.7 gene (formerly Hox 5.6). Ghox 4.7 is expressed primarily in limb buds during development and shows a striking spatial restriction to the posterior zone of the limb bud, suggesting a role in specifying anterior-posterior pattern formation. In chick, this gene also displays differences in expression between wing and leg buds, raising the possibility that it may participate in specifying limb-type identity.