Search results for "Hedgehog"
showing 10 items of 69 documents
Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human long…
2005
In this paper, we review data of recent literature on the distribution in centenarians of candidate germ-line polymorphisms that likely affect the individual chance to reach the extreme limit of human life. On the basis of previous observations on the immunology, endocrinology and cellular biology of centenarians we focused on genes that regulate immune responses and inflammation (IL-6, IL-1 cluster, IL-10), genes involved in the insulin/IGF-I signalling pathway and genes that counteract oxidative stress (PON1). On the whole, data indicate that polymorphisms of these genes likely contribute to human longevity, in accord with observations emerging from a variety of animal models, and suggest…
Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells.
2008
Neural stem cells that continue to produce neurons are retained in the adult hippocampal dentate gyrus. The mechanisms by which embryonic neural progenitors expand and transform into postnatal neural stem cells, an essential process for the continual production of neurons throughout life, remain unknown. We found that radial astrocytes, the postnatal progenitors in the dentate gyrus, failed to develop after embryonic ablation of ciliary genes or Smoothened (Smo), an essential component for Sonic hedgehog (Shh) signaling. Postnatal dentate neurogenesis failed in these mutant mice, and the dentate gyrus became severely hypotrophic. In contrast, expression of a constitutively active Smo (SmoM2…
The small heat-shock protein α B-crystallin is essential for the nuclear localization of Smad4: impact on pulmonary fibrosis
2014
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the proliferation of myofibroblasts and the accumulation of extracellular matrix (ECM) in the lungs. TGF-β1 is the major profibrotic cytokine involved in IPF and is responsible for myofibroblast proliferation and differentiation and ECM synthesis. αB-crystallin is constitutively expressed in the lungs and is inducible by stress, acts as a chaperone and is known to play a role in cell cytoskeleton architecture homeostasis. The role of αB-crystallin in fibrogenesis remains unknown. The principal signalling pathway involved in this process is the Smad-dependent pathway. We demonstrate here that αB-crystallin is stron…
A ciliopathy complex builds distal appendages to initiate ciliogenesis
2021
ABSTRACTCells inherit two centrioles, the older of which is uniquely capable of generating a cilium. Using proteomics and super-resolved imaging, we identified a module which we term DISCO (DIStal centriole COmplex). DISCO components CEP90, MNR and OFD1 underlie human ciliopathies. This complex localized to both distal centrioles and centriolar satellites, proteinaceous granules surrounding centrioles. Cells and mice lacking CEP90 or MNR did not generate cilia, failed to assemble distal appendages, and did not transduce Hedgehog signals. Disrupting the satellite pools did not affect distal appendage assembly, indicating that it is the centriolar populations of MNR and CEP90 that are critica…
Extrinsic and Intrinsic Factors Modulating Proliferation and Self-renewal of Multipotential CNS Progenitors and Adult Neural Stem Cells of the Subven…
2006
Although stem cell therapy has been proposed for therapeutic strategies aimed at repairing functions, it is important to realize that as yet, relatively little is known about the behavior of embryonic and adult stem cells in terms of responsiveness to extracellular cues and intracellular signaling molecules.
Successive specification ofDrosophilaneuroblasts NB 6-4 and NB 7-3 depends on interaction of the segment polarity geneswingless,gooseberryandnaked cu…
2001
The Drosophila central nervous system derives from neural precursor cells, the neuroblasts (NBs), which are born from the neuroectoderm by the process of delamination. Each NB has a unique identity, which is revealed by the production of a characteristic cell lineage and a specific set of molecular markers it expresses. These NBs delaminate at different but reproducible time points during neurogenesis (S1-S5) and it has been shown for early delaminating NBs (S1/S2) that their identities depend on positional information conferred by segment polarity genes and dorsoventral patterning genes. We have studied mechanisms leading to the fate specification of a set of late delaminating neuroblasts,…
Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool
2008
Cerebellar granule cell precursors (GCPs), which give rise to the most abundant neuronal type in the mammalian brain, arise from a restricted pool of primary progenitors in the rhombic lip (RL). Sonic hedgehog (Shh) secreted by developing Purkinje cells is essential for the expansion of GCPs and for cerebellar morphogenesis. Recent studies have shown that the primary cilium concentrates components of Shh signaling and that this structure is required for Shh signaling. GCPs have a primary cilium on their surface [Del Cerro, M.P., Snider, R.S. (1972). Studies on the developing cerebellum. II. The ultrastructure of the external granular layer. J Comp Neurol 144, 131-64.]. Here, we show that 1)…
Epidemiology ofSalmonella typhimurium: ribosomal DNA analysis of strains from human and animal sources
1993
SUMMARYSalmonella typhimuriumis the most frequently identified serovar ofSalmonellain Italy. This serovar is characterized by the widespread dissemination among human and non-human sources of phenotypically and genetically well-differentiated clones.In this study 457 strains ofS. typhimuriumisolated in Italy in the years 1982–91 from human and animal sources were submitted to characterization by the rDNA fingerprinting technique. Application of this typing method, after digestion of chromosomal DNA withHincII endonuclease, confirmed the greatest genetic differentiation of clones ofS. typhimurium, allowing reliable identification of 45 rDNA patterns linked into 9 major clusters. rDNA pattern…
TALPID3/KIAA0586 regulates multiple aspects of neuromuscular patterning during gastrointestinal development in animal models and human
2021
ABSTRACTTALPID3/KIAA0586 is an evolutionary conserved protein, which plays an essential role in protein trafficking. Its role during gastrointestinal (GI) and enteric nervous system (ENS) development has not been studied previously. Here, we analysed chicken, mouse and human embryonic GI tissues with TALPID3 mutations. The GI tract of TALPID3 chicken embryos was shortened and malformed. Histologically, the gut smooth muscle was mispatterned and enteric neural crest cells were scattered throughout the gut wall. Analysis of the Hedgehog pathway and gut extracellular matrix provided causative reasons for these defects. Interestingly, chicken intra-species grafting experiments and a conditional…
optomotor-blind suppresses instability at the A/P compartment boundary of the Drosophila wing.
2008
Formation and function of the A/P compartment boundary of the Drosophila wing have been studied intensely. The boundary prevents mingling of A and P cells, is characterized by an expression discontinuity of several genes like engrailed, Cubitus interruptus, hedgehog and decapentaplegic and is essential for patterning the wing. Compared with segmental or compartmental boundaries in several other systems which generally manifest as folds or clefts, the wing A/P boundary is morphologically inconspicuous in both the larval and adult stage. We show here that the Drosophila wing A/P boundary, too, is susceptible to fold and cleft formation and that these processes are suppressed by the T-box tran…