PubMed Health⌕ Search

Biomedical subjects

Shai Shaham

Publications and source records attributed to Shai Shaham.

10 recordsLinked to original sources
PubMed2007

A morphologically conserved nonapoptotic program promotes linker cell death in Caenorhabditis elegans.

Apoptosis, cell death characterized by stereotypical morphological features, requires caspase proteases. Nonapoptotic, caspase-independent cell death pathways have been postulated; however, little is known about their molecular constituents or in vivo functions. Here, we show that death of the Caenorhabditis elegans linker cell during development is independent of the ced-3 caspase and all known cell death genes. The linker cell employs a cell-autonomous death program, and a previously undescribed engulfment program is required for its clearance. Dying linker cells display nonapoptotic features, including nuclear crenellation, absence of chromatin condensation, organelle swelling, and accumulation of cytoplasmic membrane-bound structures. Similar features are seen during developmental death of neurons in the vertebrate spinal cord and ciliary ganglia. Linker cell death is controlled by the microRNA let-7 and Zn-finger protein LIN-29, components of the C. elegans developmental timing pathway. We propose that the program executing linker cell death is conserved and used during vertebrate development.

Animals↗
PubMed2006

Glia-neuron interactions in the nervous system of Caenorhabditis elegans.

A century and a half after first being described, glia are beginning to reveal their intricate and important roles in nervous system development and function. Recent studies in the nematode Caenorhabditis elegans suggest that this invertebrate will provide important insight into these roles. Studies of C. elegans have revealed a connection between glial ensheathment of neurons and tubulogenesis, have uncovered glial roles in neurite growth, navigation, and function, and have demonstrated roles for glia and glia-like cells in synapse formation and function. Given the conservation of basic anatomical, functional and molecular features of the nervous systems between C. elegans and vertebrates, these recent advances are likely to be informative in describing nervous system assembly and function in all organisms possessing a nervous system.

Animals↗
PubMed2006

The Dynami(n)cs of cell corpse engulfment.

Engulfment of dying cells plays an important role during animal development and homeostasis, and several proteins involved in this process are known. However, the cell biology underlying phagocyte arm extension and cell corpse degradation is not well understood. A study published in this issue of Developmental Cell (Yu et al., 2006) now demonstrates an important role for the GTPase dynamin in these events.

Animals↗
PubMed2005

Functional genomics of the cilium, a sensory organelle.

Cilia and flagella play important roles in many physiological processes, including cell and fluid movement, sensory perception, and development. The biogenesis and maintenance of cilia depend on intraflagellar transport (IFT), a motility process that operates bidirectionally along the ciliary axoneme. Disruption in IFT and cilia function causes several human disorders, including polycystic kidneys, retinal dystrophy, neurosensory impairment, and Bardet-Biedl syndrome (BBS). To uncover new ciliary components, including IFT proteins, we compared C. elegans ciliated neuronal and nonciliated cells through serial analysis of gene expression (SAGE) and screened for genes potentially regulated by the ciliogenic transcription factor, DAF-19. Using these complementary approaches, we identified numerous candidate ciliary genes and confirmed the ciliated-cell-specific expression of 14 novel genes. One of these, C27H5.7a, encodes a ciliary protein that undergoes IFT. As with other IFT proteins, its ciliary localization and transport is disrupted by mutations in IFT and bbs genes. Furthermore, we demonstrate that the ciliary structural defect of C. elegans dyf-13(mn396) mutants is caused by a mutation in C27H5.7a. Together, our findings help define a ciliary transcriptome and suggest that DYF-13, an evolutionarily conserved protein, is a novel core IFT component required for cilia function.

Animals↗
PubMed2005

C. elegans daf-6 encodes a patched-related protein required for lumen formation.

Sensory organs are often composed of neuronal sensory endings accommodated in a lumen formed by ensheathing epithelia or glia. Here we show that lumen formation in the C. elegans amphid sensory organ requires the gene daf-6. daf-6 encodes a Patched-related protein that localizes to the luminal surfaces of the amphid channel and other C. elegans tubes. While daf-6 mutants display only amphid lumen defects, animals defective for both daf-6 and the Dispatched gene che-14 exhibit defects in all tubular structures that express daf-6. Furthermore, DAF-6 protein is mislocalized, and lumen morphogenesis is abnormal, in mutants with defective sensory neuron endings. We propose that amphid lumen morphogenesis is coordinated by neuron-derived cues and a DAF-6/CHE-14 system that regulates vesicle dynamics during tubulogenesis.

Animals↗
PubMed2005

Glia-neuron interactions in nervous system function and development.

Nervous systems are generally composed of two cell types-neurons and glia. Early studies of neurons revealed that these cells can conduct electrical currents, immediately implying that they have roles in the relay of information throughout the nervous system. Roles for glia have, until recently, remained obscure. The importance of glia in regulating neuronal survival had been long recognized. However, this trophic support function has hampered attempts to address additional, more active functions of these cells in the nervous system. In this chapter, recent efforts to reveal some of these additional functions are described. Evidence supporting a role for glia in synaptic development and activity is presented, as well as experiments suggesting glial guidance of neuronal migration and process outgrowth. Roles for glia in influencing the electrical activity of neurons are also discussed. Finally, an exciting system is described for studying glial cells in the nematode C. elegans, in which recent studies suggest that glia are not required for neuronal viability.

Animals↗
PubMed2004

Death without caspases, caspases without death.

Apoptosis is a conserved cell-death process displaying characteristic morphological and molecular changes including activation of caspase proteases. Recent work challenges the accepted roles of these proteases. New investigations in mice and the nematode Caenorhabditis elegans suggest that there could be caspase-independent pathways leading to cell death. In addition, another type of cell death displaying autophagic features might depend on caspases. Recent studies also indicate that caspase activation does not always lead to cell death and, instead, might be important for cell differentiation. Here, we review recent evidence for both the expanded roles of caspases and the existence of caspase-independent cell-death processes. We suggest that cellular context plays an important role in defining the consequences of caspase activation.

Animals↗
PubMed2003

Apoptosis: a process with a (beta)NAC for complexity.

Most programmed cell deaths in the nematode C. elegans require ced-3 caspase activity. In a recent paper, reveal a new C. elegans death inhibitor, icd-1, whose loss can promote apoptosis independently of ced-3.

Animals↗
PubMed2002

Control of neuronal subtype identity by the C. elegans ARID protein CFI-1.

The Caenorhabditis elegans hermaphrodite nervous system is composed of 302 neurons that fall into at least 118 diverse classes. Here we describe cfi-1, a gene that contributes to the development of neuronal diversity. cfi-1 promotes appropriate differentiation of the URA sensory neurons and inhibits URA from expressing the male-specific CEM neuronal fate. The UNC-86 POU homeodomain protein is present in CEM and URA neurons, and can promote expression of CEM-specific genes in both CEM and URA, but CFI-1 inhibits expression of these genes in the URA cells. cfi-1 also promotes appropriate differentiation and glutamate receptor expression in the AVD and PVC interneurons. cfi-1 encodes a conserved neuron- and muscle-restricted DNA-binding protein containing an A/T rich interaction domain (ARID). ARID proteins regulate early patterning and muscle fate in Drosophila, but they have not previously been implicated in the control of neuronal subtype identity.

Animals↗