发育中的重要调控基因——Pax9

Pax9是Pax基因家族的一员,广泛地参与脊椎和无脊椎支物胚胎发育过程中众多器官的形成,基因的部分缺失或完全缺陷皆可导致个体众多器官的发育缺陷甚至个体死亡。Pax9是多种组织的标志物,在间充质而非上皮细胞中起重要调控作用。     

Pax基因功能及其选择性剪接的研究进展

Pax基因家族编码的蛋白是一组极为重要的转录调控因子,在胚胎发育的器官形成中扮演重要角色,其主要功能包括：调控细胞增殖、促进细胞自我更新、诱导前体细胞定向转移以及改变特异细胞系的分化方向。目前已知,Pax基因的非正常表达是多种先天性疾病的主要诱因。Pax基因的选择性剪接体通常具有一定的空间特异性,每种剪接体都有其主要作用的靶位和信号通路。文章简述了Pax基因的相关背景知识,详细介绍Paxl—Pax9调控在胚胎组织发育中的各项功能,并列举了现已确定的Pax基因在不同物种中的选择性剪接产物。     

Hedgehog信号通路在胚胎发育过程中的调控作用

Hedgehog信号通路首次在果蝇体内被发现,进化上呈高度保守状态。该通路在胚胎发育、机体组织器官的形成过程中发挥了重要作用,它的异常调节会导致一系列严重的疾病。本文主要就Hedgehog信号通路对神经系统、骨骼系统、消化系统、肺、颅面部发育的调控作用作一综述。     

果蝇心脏发育基因调控的研究进展

果蝇心脏的发育是一个受到一系列基因共同调控的复杂过程,这些基因在脊椎动物和无脊椎动物果蝇中具有惊人的相似性,对于它们功能的研究将有助于揭示人类心脏发育的过程及分子控制机理.通过将果蝇作为一种重要的模式动物,对心脏发育基因调控的研究进展作一综述.     

舌的发育及其调控机制

舌是参与咀嚼、吸允、吞咽、发音等功能的重要器官。舌发育异常会导致无舌、小舌、舌裂、结舌、巨舌症、腭裂等严重的先天舌发育缺陷疾病。发育完全的舌由肌肉组织、结缔组织、黏膜组织及血管组成。调控舌发育的基因有Pax3/Pax7、Dlx基因家族、TGF-β家族和FGF等,同时还受Shh与Wnt等信号通路调控。舌发育分子调控机制的研究对相关舌发育畸形疾病的诊断与治疗有重要意义。     

昆虫分子生物学的一些进展：胚胎发育飞丝蛋白与可诱导的抗菌蛋白

胚胎发育中的基因调控 从一个受精卵发育成一个多细胞的个体,涉及许多基因,其表达有时间上的程序和空间上的限制。调控果蝇(Drosophila melanogaster)胚胎发育的基因已研究得很详细,包括三大类调控基因——母体基因、分节基因和同源异形基因。在早期发育中,这三类基因相继起作用,前一类基因的产物依次调节下类基因的表达,组成一个调控等级网(或称     

Hippo信号通路生物学作用研究进展

Hippo信号通路是20世纪末在黑腹果蝇中进行基因筛选时发现的,该通路受各种生化、物理和结构信号的影响,调控细胞生长、分化,组织和器官发育以及内环境稳态等基本生物学过程。研究表明Hippo信号通路失调会引起一系列疾病的发生。本文阐述了目前Hippo信号通路在胚胎发育、器官和组织稳态调节、肿瘤的发生发展和细胞自噬等一系列生物学过程以及靶向治疗中的研究进展,其中Hippo信号通路通过细胞自噬来维持机体细胞内环境稳态成为新的研究热点。对该通路的功能和调控机制的深入研究也为组织器官修复再生医学及癌症治疗提供参考。     

GATA转录因子家族在细胞命运调控中的作用

在胚胎发育过程中,组织器官的形成依赖于干细胞在空间与时间上正确的定向分化、增殖,以及中间细胞的凋亡.这一细胞命运决定的过程必须被严格精确地调控,从而保证胚胎发育过程中组织器官形成得以顺利地进行.在此过程中,GATA转录因子家族扮演了不可或缺的角色,它们在胚层分化、造血系统和心脏形成、胸腺和肠道发育以及肿瘤发生中都起到了重要的作用.本文结合目前对GATA转录因子家族的研究和本课题组实验结果,介绍其在干细胞分化和维持,以及它们在细胞重编程中所起的作用.     

同源异型框基因与动物早期发育

同源异型框基因广泛存在于真核生物中,编码一类转录调节蛋白。同源异型框基因在动物早期发育的基因调控中起着非常重要的作用。在动物胚胎发育过程中,同源异型框基因的表达具有复杂的时空模式和调控系统。Antp族基因对于早期胚胎发育中的模式建成,器官分化等具有重要意义。     

SonicHedgehog基因及其在发育过程中的调控作用

SonicHedgehog（Shh）基因属于Hedgehog（Hh）基因家族,该家族最早在果蝇体内被发现,进化上呈高度保守状态。SonicHedgehog定位在7号染色体长臂远端（7q36）,其通过细胞表面特殊受体Patched（Ptc）和sInoothened（smo）被接收和传导,从而激活锌指蛋白Ci／Gli家族。SonicHedgehog基因作为重要的形态发生素,在胚胎发育、机体器官组织形成的过程中发挥了重要的作用,它的缺失或者失活会导致一系列严重的遗传疾病。其与体节、神经管、消化道、头面部、上下肢芽的发育以及肿瘤形成等有密切关系。本文主要就SonicHedgehog基因及其在发育中的调控作用作一综述。     

Dach1, a vertebrate homologue of Drosophila dachshund, is expressed in the developing eye and ear of both chick and mouse and is regulated independently of Pax and Eya genes.

We have cloned a chick homologue of Drosophila dachshund (dac), termed Dach1. Dach1 is the orthologue of mouse and human Dac/Dach (hereafter referred to as Dach1). We show that chick Dach1 is expressed in a variety of sites during embryonic development, including the eye and ear. Previous work has demonstrated the existence of a functional network and genetic regulatory hierarchy in Drosophila in which eyeless (ey, the Pax6 orthologue), eyes absent (eya), and dac operate together to regulate Drosophila eye development, and that ey regulates the expression of eya and dac. We find that in the developing eye of both chick and mouse, expression domains of Dach1 overlap with those of Pax6, a gene required for normal eye development. Similarly, in the developing ear of both mouse and chick, Dach1 expression overlaps with the expression of another Pax gene, Pax2. In the mouse, Dach1 expression in the developing ear also overlaps with the expression of Eya1 (an eya homologue). Both Pax2 and Eya1 are required for normal ear development. Our expression studies suggest that the Drosophila Pax-eya-dac regulatory network may be evolutionarily conserved such that Pax genes, Eya1, and Dach1 may function together in vertebrates to regulate neural development. To address the further possibility that a regulatory hierarchy exists between Pax, Eya, and Dach genes, we have examined the expression of mouse Dach1 in Pax6, Pax2 and Eya1 mutant backgrounds. Our results indicate that Pax6, Pax2, and Eya1 do not regulate Dach1 expression through a simple linear hierarchy.     

EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification

The Drosophila compound eye is specified by the concerted action of seven nuclear factors that include Eyeless/Pax6. These factors have been called "master control" proteins because loss-of-function mutants lack eyes and ectopic expression can direct ectopic eye development. However, inactivation of these genes does not cause the presumptive eye to change identity. Surprisingly, we find that several of these eye specification genes are not coexpressed in the same embryonic cells-or even in the presumptive eye. We demonstrate that the EGF Receptor and Notch signaling pathways have homeotic functions that are genetically upstream of the eye specification genes, and show that specification occurs much later than previously thought-not during embryonic development but in the second larval stage.     

Characterization of mouse Dach2, a homologue of Drosophila dachshund

The Drosophila genes eyeless, eyes absent, sine oculis and dachshund cooperate as components of a network to control retinal determination. Vertebrate homologues of these genes have been identified and implicated in the control of cell fate. We present the cloning and characterization of mouse Dach2, a homologue of dachshund. In situ hybridization studies demonstrate Dach2 expression in embryonic nervous tissues, sensory organs and limbs. This pattern is similar to mouse Dach1, suggesting a partially redundant role for these genes during development. In addition, we determine that Dach2 expression in the forebrain of Pax6 mutants and dermamyotome of Pax3 mutants is not detectably altered. Finally, genetic mapping experiments place mouse Dach2 on the X chromosome between Xist and Esx1. The identification of human DACH2 sequences at Xq21 suggests a possible role for this gene in Allan-Herndon syndrome, Miles-Carpenter syndrome, X-linked cleft palate and/or Megalocornea.     

Functional conservation of the Drosophila gooseberry gene and its evolutionary alleles

The Drosophila Pax gene gooseberry (gsb) is required for development of the larval cuticle and CNS, survival to adulthood, and male fertility. These functions can be rescued in gsb mutants by two gsb evolutionary alleles, gsb-Prd and gsb-Pax3, which express the Drosophila Paired and mouse Pax3 proteins under the control of gooseberry cis-regulatory region. Therefore, both Paired and Pax3 proteins have conserved all the Gsb functions that are required for survival of embryos to fertile adults, despite the divergent primary sequences in their C-terminal halves. As gsb-Prd and gsb-Pax3 uncover a gsb function involved in male fertility, construction of evolutionary alleles may provide a powerful strategy to dissect hitherto unknown gene functions. Our results provide further evidence for the essential role of cis-regulatory regions in the functional diversification of duplicated genes during evolution.     

The Trichoplax PaxB gene: a putative Proto-PaxA/B/C gene predating the origin of nerve and sensory cells

Pax genes play key regulatory roles in embryonic and sensory organ development in metazoans but their evolution and ancestral functions remain widely unresolved. We have isolated a Pax gene from Placozoa, beside Porifera the only metazoan phylum that completely lacks nerve and sensory cells or organs. These simplest known metazoans also lack any kind of symmetry, organs, extracellular matrix, basal lamina, muscle cells, and main body axis. The isolated Pax gene from Trichoplax adhaerens harbors a paired domain, an octapeptide, and a full-length homeodomain. It displays structural features not only of PaxB and Pax2/5/8-like genes but also of PaxC and Pax6 genes. Conserved splice sites between Placozoa, Cnidaria, and triploblasts, mark the ancient origin of intron structures. Phylogenetic analyses demonstrate that the Trichoplax PaxB gene, TriPaxB, is basal not only to all other known PaxB genes but also to PaxA and PaxC genes and their relatives in triploblasts (namely Pax2/5/8, Pax4/6, and Poxneuro). TriPaxB is expressed in distinct cell patches near the outer edge of the animal body, where undifferentiated and possibly multipotent cells are found. This expression pattern indicates a developmental role in cell-type specification and/or differentiation, probably in specifying-determining fiber cells, which are regarded as proto-neural/muscle cells in Trichoplax. While PaxB, Pax2/5/8, and Pax6 genes have been linked to nerve cell and sensory system/organ development in virtually all animals investigated so far, our study suggests that Pax genes predate the origin of nerve and sensory cells.     

Redeployment of the Six genes in evolution

It has become clear that during evolution, efficient molecular mechanisms are used over and over again to achieve various patterning tasks. The Six gene story illustrates a new aspect of the molecular conservation during embryogenesis. Members of the Six gene family have been identified on the basis of sequence homology with Drosophila sine oculis gene, which acts within a network of genes including eyeless (Pax family), eyes absent (Eya family) and dachshund (Dach family) to trigger compound eye organogenesis. Some aspects of the regulatory complex operating in Drosophila appear to be conserved during vertebrate eye patterning, but also for other differentiation processes. In this regard, Six1 is required nonetheless during myogenesis, but also for kidney, thymus, inner ear, nose, lacrimal and salivary gland organogenesis. These phenotypes are reminiscent of those previously described for Eya and Pax mutants, suggesting a functional link between these factors during mammalian organogenesis.