Sufu defines the balance of hindbrain progenitor cells maintenance and differentiation

Suppressor of fused (Sufu) was identified as a regulator in Hedgehog signalling. Study shown that Sufu knockout mice were embryonic lethal at E9.5, exhibiting cephalic deformities, open neural tube and ventralized spinal cord resulting from ectopic Shh signalling, implying indispensable role of Sufu during development of central nervous system. Aiming to investigate the functions of Sufu in hindbrain neurogenesis, we used B2‐r4‐Cre to knock‐out Sufu in rhombomere4 (r4). We observed significant enlargement of mutant r4 size from E10.5, exhibiting more profound expansion in the dorsal region at E12.5. Accordingly, BrdU pulse labelling and sox2 staining showed region specific increased accumulation of proliferative progenitor cells, indicating differential maintenance of progenitor pools along the dorsoventral axis of r4. Tuj1 staining also showed impaired differentiation of the ectopic progenitor cells. Further analysis revealed dramatic dorsal expansion of pMN and p2 progenitor domains in mutant r4. Surprisingly, the FoxA2 positive floor plate, and the dorsal p0 domain were not severely affected, suggesting a novel domain specific regulation of neural progenitor pools by Sufu. Intriguingly, we observed spatial upregulation Gli1 and Gli2 transcription factors, selectively at the region that resides highly proliferative cells, implying that the increased cell proliferation could be caused by the changes of Gli transcription factors. Indeed, concomitant deletion of Gli2 in the Sufu mutant largely rescued the aberrant phenotypes. These findings clearly showed the requirement of Sufu to suppress Gli2 to conduct a domain specific regulation of hindbrain progenitor maintenance and differentiation. Our study demonstrates novel function of Sufu to ensure a tightly controlled progenitor pools maintenance and differentiation, mainly achieve by suppressing Gli2 activation.postprin

Sufu and Gli3 repressor mediate the temporal basal-to-apical progression of hair cell differentiation in mammalian cochleae

Poster presentation - Theme 3: Development & stem cellsThe Sonic Hedgehog pathway plays important roles in mammalian inner ear development. Mutations of Shh, Smo and Gli3 lead to severe defects in mouse inner ear morphogenesis. However, knockout of Gli2 does not affect inner ear morphology or cochlear hair cell differentiation, suggesting that the Gli repressor function may be required for Hedgehog signaling during inner ear development. Sufu is a negative regulator of Hedgehog signaling and it functions to repress Gli activator and enhance Gli repressor ...postprin

Identification and characterization of long-range SOX9 enhancers in limb development

The transcription factor Sox9 is a master regulator of skeletogenesis. Heterozygous mutations of human SOX9 result in Campomelic Dysplasia (CD), in which affected individuals display distinct abnormalities in limbs and other skeletal assemblies. Recently, chromosomal translocations and deletions at >1Mb from SOX9 have been detected in some CD patients, suggesting the requirement of long‐range regulatory elements in mediating both spatiotemporal and dosage of Sox9 during limb development. To this end, we exploited several published ChIP‐Seq data, and identified nine, evolutionarily conserved, putative limb enhancers of SOX9, namely E1Sox9 to E9Sox9. Transgenic mouse embryos carrying E1Sox9‐driven LacZ reporter showed discrete transgene expression at the pre‐scapular domain where endogenous Sox9 is also expressed. Bioinformatic analyses on our candidate enhancers result in the identification of several signaling effector binding motifs, and indeed, we revealed that BMP‐Smad and Shh‐Gli pathways are possible upstream regulatory networks that govern the spatiotemporal and dosage of limb Sox9 expression via our predicted enhancers, respectively. Our results unveil the underlying molecular control in governing the complex patterning of Sox9 expression in the developing limb, and provide new molecular insight to the etiology of CD syndrome.postprin

The roles of Irx3 and Irx5 in mammalian inner ear development

Iroquois genes encode a family of transcription factors containing TALE class homeodomain. They are regarded as prepatterning genes in Drosophila sensory organ development. There are six members (Irx1Irx6) of Iroquois genes in mouse and human. Irx3 and Irx5 are linked genes on mouse chromosome 8, which are involved in many mammalian developmental processes. However, the roles of Irx3 and Irx5 in mammalian hearing loss are poorly understood. To identify the function of these two genes in inner ear development, we have investigated two reporter knock‐in mouse mutants: Irx3lacZ, Irx5EGFP, and a double knock‐out mutant: Irx3/5‐/‐. Irx3 and Irx5 have overlapping expression domains in the developing inner ear. Physiological tests indicated that the Irx3lacZ and Irx5EGFP mutant mice displayed hearing defect, while Irx3/5‐/‐ mice were embryonic lethal. Although paint filling analysis showed the normal cochlea morphology of Irx3lacZ and Irx5EGFP mutant mice, ectopic inner hair cells have been discovered in the organ of Corti. Interestingly, the cochlear duct of Irx3/5‐/‐ mice was enlarged and shortened, and the basal part of the cochlea was fused with the saccule. There were also numerous vestibular‐like ectopic hair cells surrounded by ectopic Sox2‐positive cells in the greater epithelial ridge of cochlea. The organ of Corti was malformed with neither hair cell differentiation nor supporting cell differentiation at E16.5. In summary, our results indicate that Irx3 and Irx5 cooperatively pattern the boundary between the vestibule and the cochlea and they are important for the cochlear sensory neural cell specification.postprin

The roles of Irx3 and Irx5 genes in inner ear sensorineural patterning

Poster Presentation - Theme 3: Development & stem cellsIrx3 and Irx5 are members of the Iroquois family TALE homeodomain transcription factors, which function as patterning genes in multiple developmental processes. In the developing limb bud, Irx3 and Irx5 are critical for establishing early AP polarity and digit specification. In the developing inner ear, we have found that Irx3/5 compound mutant displayed enlarged cochlear lumen, abnormal spiral ganglion, and fusion of inner ear sensory regions. These abnormal phenotypes suggest that Irx3 and Irx5 may have essential role in early inner …postprin

Burkholderia pseudomallei in soil samples from an oceanarium in Hong Kong detected using a sensitive PCR assay

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Bioactivity-guided identification and cell signaling technology to delineate the immunomodulatory effects of Panax ginseng on human promonocytic U937 cells

<p>Abstract</p> <p>Background</p> <p>Ginseng is believed to have beneficial effects against human diseases, and its active components, ginsenosides, may play critical roles in its diverse physiological actions. However, the mechanisms underlying ginseng's effects remain to be investigated. We hypothesize some biological effects of ginseng are due to its anti-inflammatory effects.</p> <p>Methods</p> <p>Human promonocytic U937 cells were used to investigate the immunomodulatory effects of ginseng following TNF-α treatment. A global gene expression profile was obtained by using genechip analysis, and specific cytokine expression was measured by quantitative RT-PCR and ELISA. HPLC was used to define the composition of ginsenosides in 70% ethanol-water extracts of ginseng. Activation of signalling kinases was examined by Western blot analysis.</p> <p>Results</p> <p>Seventy percent ethanol-water extracts of ginseng significantly inhibited the transcription and secretion of CXCL-10 following TNF-α stimulation. Nine ginsenosides including Rb₁, Rb₂, Rc, Rd, Re, Rf, Rg₁, Rg₃and Rh₁were identified in our extract by HPLC. Seven out of nine ginsenosides could significantly inhibit TNF-α-induced CXCL-10 expression in U937 cells and give comparable inhibition of CXCL-10 transcription to those with the extract. However, the CXCL-10 suppressive effect of individual ginsenosides was less than that of the crude extract or the mixture of ginsenosides. The CXCL-10 suppression can be correlated with the inactivation of ERK1/2 pathways by ginseng.</p> <p>Conclusion</p> <p>We showed ginseng suppressed part of the TNF-α-inducible cytokines and signalling proteins in promonocytic cells, suggesting that it exerts its anti-inflammatory property targeting at different levels of TNF-α activity. The anti-inflammatory role of ginseng may be due to the combined effects of ginsenosides, contributing in part to the diverse actions of ginseng in humans.</p

Discovery of an X-ray Emitting Contact Binary System 2MASS J11201034-2201340

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Optimal Receiver Antenna Location in Indoor Environment Using Dynamic Differential Evolution and Genetic Algorithm

[[abstract]]Using the impulse responses of these multipath channels, the bit error rate (BER) performance for binary pulse amplitude modulation impulse radio ultra-wideband communication system is calculated. The optimization location of receiving antenna is investigated by dynamic differential evolution (DDE) and genetic algorithm (GA) to minimize the outage probability. Numerical results show that the performance for reducing BER and outage probability by DDE algorithm is better than that by GA.[[notice]]補正完畢[[incitationindex]]SCI[[booktype]]紙本[[booktype]]電子