果蝇体极性基因网络的稳定性分析

果蝇的全基因组的序列测定早已完成,但是,对于基因之间是如何相互调控以实现复杂的生物功能,还需要深入的研究.认识并解析复杂的基因调控网络的构成和动力学机制,已成为现代生命科学中的前沿课题之一.在本文中,我们重点研究了果蝇的胚胎发育过程中图式形成的体极性基因网络调控.这一调控是通过相邻细胞中的基因网络的相互影响而达成的.本文主要考察这种基因网络调控对于初始条件的稳定性,以此说明生物胚胎发育对于初始条件的相对稳定性.我们发现该调控系统对于特定位置的干扰有极好的稳定性,对于整个系统的小干扰有良好的稳定性.     

A Drosophila Minute gene encodes a ribosomal protein

Minute genes have long constituted a special problem in Drosophila genetics. For at least 50-60 different genes scattered throughout the genome, dominant mutations and/or deficiencies have been recognized which result in a common phenotype consisting of short thin bristles, slow development, reduced viability, rough eyes, small body size and etched tergites. Schultz proposed that the Minute loci encode similar but separate functions involved in growth and division common to all cells. Atwood and Ritossa suggested that Minute loci encode components of the protein synthetic machinery, specifically the transfer RNA genes; this now seems unlikely on grounds of both mapping and mutability studies. More recently, we and others suggested that the Minute loci are ribosomal protein genes. We report here that transformation with a cloned 3.3-kilobase (kb) region containing the gene encoding the large subunit ribosomal protein 49 (rp49) suppresses the dominant phenotypes of Minute (3)99D, a previously undescribed Minute associated with a chromosomal deficiency of the 99D interval. This activity is specific to the 99D Minute as it does not suppress other Minute loci elsewhere in the genome. This result provides direct evidence that the Minute locus at the 99D interval encodes the ribosomal protein 49.     

Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria

Methotrexate, a folate antagonist, blocks import into mitochondria of mouse dihydrofolate reductase fused to a mitochondrial presequence. Methotrexate does not mask the presequence, but stabilizes the dihydrofolate reductase moiety. It does not inhibit import of the authentic precursor from which the presequence is derived. This suggests that dihydrofolate reductase must at least partly unfold in order to be transported across mitochondrial membranes.     

Maternal control of Drosophila segmentation gene expression

Several genes have been identified that are involved in establishing the segmented body pattern during development of the fruit-fly Drosophila melanogaster. These fall into several classes on the basis of the kind of alteration to the wild-type segmentation pattern observed in mutant embryos. For example, mutations of the pair-rule class, such as fushi tarazu (ftz), cause the deletion of pattern elements with a two-segment periodicity; those of the gap class, such as knirps, cause the deletion of contiguous groups of segments. The availability of antibodies against the ftz protein has allowed its spatial pattern of expression to be studied during the development of wild-type and mutant embryos. The aim of the latter kind of experiment is to investigate possible interactions between these important genes. We have recently reported that knirps mutations cause a striking alteration to the pattern of transverse stripes of ftz expression usually seen during embryogenesis. Knirps is a zygotically-expressed gene, but recently a class of maternally-active genes has been identified that causes similar defects in pattern formation. We have now investigated the pattern of ftz expression in mutants of this class and have found that while they do have features seen in knirps mutants, they also exhibit significant differences between the different mutations reflecting the distinct but overlapping domains of gene activity. These observations demonstrate that maternally-active segmentation genes regulate zygotic gene expression, and that some of their effects on ftz may be directed through the knirps gene.     

A gene affecting the specificity of the chemosensory neurons of Drosophila

The sensilla on the proboscis and tarsi of Drosophila contain five neurons, four chemosensory and one mechanosensory. The sugar-sensitive neuron, designated S, carries independent acceptor sites for pyranose, furanose and trehalose. Two others, L1 and L2, respond to salts. The fourth neuron, W, is inhibited by salts and sugars, and is believed to mediate detection of water. We describe here a gene in which mutations alter the neurons in such a way that the S cell is excited by salts. As a result, the mutant flies are strongly attracted by NaCl at concentrations which are repellent to the wild type. To our knowledge, this is the first instance of a mutation which changes the specificity of the chemosensory neurons.     

Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease

In idiopathic Parkinson's disease massive cell death occurs in the dopamine-containing substantia nigra. A link between the vulnerability of nigral neurons and the prominent pigmentation of the substantia nigra, though long suspected, has not been proved. This possibility is supported by evidence that N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite MPP+, the latter of which causes destruction of nigral neurons, bind to neuromelanin. We have directly tested this hypothesis by a quantitative analysis of neuromelanin-pigmented neurons in control and parkinsonian midbrains. The findings demonstrate first that the dopamine-containing cell groups of the normal human midbrain differ markedly from each other in the percentage of neuromelanin-pigmented neurons they contain. Second, the estimated cell loss in these cell groups in Parkinson's disease is directly correlated (r = 0.97, P = 0.0057) with the percentage of neuromelanin-pigmented neurons normally present in them. Third, within each cell group in the Parkinson's brains, there is greater relative sparing of non-pigmented than of neuromelanin-pigmented neurons. This evidence suggests a selective vulnerability of the neuromelanin-pigmented subpopulation of dopamine-containing mesencephalic neurons in Parkinson's disease.     

Connectivity of chemosensory neurons is controlled by the gene poxn in Drosophila.

The function of the nervous system depends on the formation of a net of appropriate connections, but little is known of the genetic program underlying this process. In Drosophila two genes that specify different types of sense organs have been identified: cut (ct), which specifies the formation of external sense organs as opposed to chordotonal organs, and pox-neuro (poxn), which specifies the formation of poly-innervated (chemosensory) organs as opposed to mono-innervated (mechanosensory) organs. Whether these genes are also involved in specifying the connectivity of the corresponding neurons is not known. The larval sense organs are unsuitable for analysis of the axonal pathway and connections and so we have investigated the effect of poxn on the adult. Here we show that overexpression of poxn induces the morphological transformation of mechanosensory into chemosensory bristles on the legs and that the neurons innervating the morphologically transformed bristles follow pathways and establish connections that are appropriate for chemosensory bristles.     

The Caenorhabditis elegans lin-12 gene encodes a transmembrane protein with overall similarity to Drosophila Notch

The lin-12 gene seems to control certain binary decisions during Caenorhabditis elegans development, from genetic and anatomical studies of lin-12 mutants that have either elevated or reduced levels of lin-12 activity. We report here the complete DNA sequence of lin-12: 13.5 kilobases (kb) derived from genomic clones and 4.5 kb from complementary DNA clones. It is of interest that the predicted product is a putative transmembrane protein, given that many of the decisions controlled by lin-12 activity require cell-cell interactions for the correct choice of cell fate. In addition, the predicted lin-12 product may be classified into several regions, based on amino acid sequence similarities to other proteins. These include extensive overall sequence similarity to the Drosophila Notch protein, which also is involved in cell-cell interactions that specify cell fate; a repeated motif found in proteins encoded by the yeast cell-cycle control genes cdc10 (Schizosaccharomyces pombe) and SWI6 (Saccharomyces cerevisiae); and a repeated motif exemplified by epidermal growth factor, found in many mammalian proteins.