Genetik Ufku

Expression of the eGFP::I-PpoI fusion protein in Anopheles gambiae testes.

Pictured is a confocal image of a mosquito testicle stained for DNA (with DAPI, shown in red) overlaid with the expression pattern of the eGFP-tagged I-PpoI endonuclease protein (shown in green). The testis hub region (lower right part of the picture) does not stain for eGFP, suggesting that stem cells are not affected by the potentially toxic endonuclease. Expression of the protein during later stages of spermatogenesis induced dominant male sterility and sex chromosome transmission ratio distortion, without disrupting the production of functional sperm (see Windbichler et al., doi:10.1371/journal.pgen.1000291).

Image Credit: Image generated by Philippos Aris Papathanos (Imperial College, London).

by John A. Follit, Jovenal T. San Agustin, Fenghui Xu, Julie A. Jonassen, Rajeev Samtani, Cecilia W. Lo, Gregory J. Pazour

Author Summary

The primary cilium is a sensory organelle used by cells to monitor the extracellular environment. In mouse, severe defects in primary cilia lead to embryonic lethality while less severe defects cause a pleiotrophic phenotype that includes cystic kidney disease, retinal degeneration, obesity, and hydrocephaly, among others. The sensory functions of cilia rely on proteins localized to the ciliary membrane, which is continuous with the plasma membrane of the cell. Cells have the ability to specifically localize proteins to the ciliary membrane to the exclusion of the rest of the plasma membrane. Little is known about how this is accomplished. In prior work, we showed that the ciliary assembly protein IFT20 is localized to the Golgi complex, in addition to the cilium, and we proposed that it is involved in sorting or transport of membrane proteins to the cilium. In this work, we show that IFT20 is anchored to the Golgi complex by the golgin GMAP210. Mice defective in GMAP210 die at birth with lung and heart defects. Cells from these animals have ciliary defects, suggesting that IFT20 and GMAP210 function together at the Golgi complex in the trafficking of ciliary membrane proteins.

by David Grote, Sami Kamel Boualia, Abdallah Souabni, Calli Merkel, Xuan Chi, Frank Costantini, Thomas Carroll, Maxime Bouchard

Author Summary

In humans, kidney development originates during embryonic development by the sprouting of an epithelial bud—called the ureteric bud—from a simple epithelial structure—the nephric duct. The ureteric bud quickly grows and branches in a treelike fashion to form the kidney collecting duct system, while the emerging ureteric tips induce nephron differentiation. One of the most important steps during kidney development is the positioning of a single ureteric bud along the nephric duct, since mutations of genes implicated in this process lead to severe urogenital malformations. In this study, we identified the Gata3 protein as a crucial regulator of ureteric bud positioning by using genetically modified mice. Deleting the Gata3 gene in the mouse resulted in the development of multiple kidneys emerging at improper positions. We show that this defect was caused by a hypersensitivity of nephric duct cells in their response to local growth signals. Interestingly, this phenomenon was partly triggered by premature differentiation of a subset of nephric duct cells. Furthermore, we report a genetic pathway in which Wnt/β-catenin signaling activates the Gata3 gene, which in turn positively regulates the Ret gene. In summary, we introduce a mouse model system that can be used to study human birth defects affecting the urogenital system.

by Alexis S. Hill, Atsuo Nishino, Koichi Nakajo, Giuxin Zhang, Jaime R. Fineman, Michael E. Selzer, Yasushi Okamura, Edward C. Cooper

Author Summary

Because nervous systems generate behavior, innovations that confer new neuronal signaling functions are important potential factors in evolution. In mammals, clustering of ion channels on nerves is essential for electrical impulses used in rapid signaling. This channel clustering is generally absent in insects, worms, and other non-chordates. We traced the evolutionary emergence of mechanisms underlying channel clustering on nerves by analyzing the genomes of primitive chordates and studying the cellular distribution and functional properties of their channels. We found that sodium channel clustering evolved early in the chordate lineage, before the divergence of the earliest wormlike and planktonic groups (lancelets and sea squirts). Nerve fibers of the lamprey, a primitive fish, retained some invertebrate features but possessed dense sodium channel clusters like in more recently evolved vertebrates. A potassium channel clustering system evolved, after the divergence of lampreys, in a common ancestor of shark and humans. We conclude that the clustering of sodium channels on axons was the initial pivotal step in a chordate-specific series of evolutionary innovations, making nerve impulses more rapid and robust. The refinements in action potentials we have elucidated appear essential for the complex neural signaling and active behavior of vertebrates.

In plants, many patterning processes involve the phytohormone auxin, and controlling how it moves around plays a critical role in pattern formation.

Experimental data and computer modeling show that lateral root positioning can be controlled by the physical stimulus of root curvature, which triggers self-organizing alterations in auxin transport.

Targeted disruption of SUMO-specific protease 2 in mice reveals that SUMO modulation of the p53/Mdm2 pathway is pivotal for G/S transition of mitosis and endoreduplication during trophoblast development.

DNA sequence analysis of a global collection of M. tuberculosis strains reveals high functional diversity, severely reduced selective constraint, and global spread through both ancient and recent human migrations.

The transcription factor Twist-2 is a new regulator that inhibits the proliferation and differentiation of granulocyte macrophage progenitors. Twist-2 also inhibits proinflammatory cytokine production, while stimulating IL-10 by myeloid cells.

The mode of action of certain antibiotics is revealed in a study using different strains of E. coliM, which implicates mazEF-mediated cell death and the formation of reactive oxygen species.

Early neural representation of visual scenes occurs with a temporal precision on the order of 10 ms, which is precise enough to strongly drive downstream neurons in the visual pathway. Unlike individual neurons, the neural population code is largely insensitive to pronounced changes in visual contrast.

Immortalized plant cells undergo epigenomic changes, reminiscent of immortalized animal cell lines and cancer cells, accompanied by shifts in small RNA classes, implicating a role for the RNAi machinery in regulating the epigenome.

Why do some bird species lay only one egg in their nest, and others ten? An analysis combining comparative and macroecological approaches across more than half of all bird species explains the global variation in this trait with high confidence.

It isn't easy to predict how mutations will affect a host's immune response. Mutations that affect the interaction of a fly with one pathogen can increase or decrease resistance or tolerance to other pathogens.

Hybrid lethality in crosses between diploids and tetraploids, plants with whole genome duplication, is determined by an epidermal regulator expressed in the maternal tissue that envelops the seed.

A newly identified intracellular pathogen of wild-caught Caenorhabditis elegans represents a new microsporidian species that will provide a model to study this class of pathogen in humans.