Zebrafish paraxial protocadherin is a downstream target of spadetail involved in morphogenesis of gastrula mesoderm

Development ◽  
1998 ◽  
Vol 125 (17) ◽  
pp. 3389-3397 ◽  
Author(s):  
A. Yamamoto ◽  
S.L. Amacher ◽  
S.H. Kim ◽  
D. Geissert ◽  
C.B. Kimmel ◽  
...  

Zebrafish paraxial protocadherin (papc) encodes a transmembrane cell adhesion molecule (PAPC) expressed in trunk mesoderm undergoing morphogenesis. Microinjection studies with a dominant-negative secreted construct suggest that papc is required for proper dorsal convergence movements during gastrulation. Genetic studies show that papc is a close downstream target of spadetail, gene encoding a transcription factor required for mesodermal morphogenetic movements. Further, we show that the floating head homeobox gene is required in axial mesoderm to repress the expression of both spadetail and papc, promoting notochord and blocking differentiation of paraxial mesoderm. The PAPC structural cell-surface protein may provide a link between regulatory transcription factors and the actual cell biological behaviors that execute morphogenesis during gastrulation.

2018 ◽  
Vol 4 (2) ◽  
pp. e222 ◽  
Author(s):  
Claire G. Salter ◽  
Danique Beijer ◽  
Holly Hardy ◽  
Katy E.S. Barwick ◽  
Matthew Bower ◽  
...  

ObjectiveTo identify the genetic cause of disease in 2 previously unreported families with forms of distal hereditary motor neuropathies (dHMNs).MethodsThe first family comprises individuals affected by dHMN type V, which lacks the cardinal clinical feature of vocal cord paralysis characteristic of dHMN-VII observed in the second family. Next-generation sequencing was performed on the proband of each family. Variants were annotated and filtered, initially focusing on genes associated with neuropathy. Candidate variants were further investigated and confirmed by dideoxy sequence analysis and cosegregation studies. Thorough patient phenotyping was completed, comprising clinical history, examination, and neurologic investigation.ResultsdHMNs are a heterogeneous group of peripheral motor neuron disorders characterized by length-dependent neuropathy and progressive distal limb muscle weakness and wasting. We previously reported a dominant-negative frameshift mutation located in the concluding exon of the SLC5A7 gene encoding the choline transporter (CHT), leading to protein truncation, as the likely cause of dominantly-inherited dHMN-VII in an extended UK family. In this study, our genetic studies identified distinct heterozygous frameshift mutations located in the last coding exon of SLC5A7, predicted to result in the truncation of the CHT C-terminus, as the likely cause of the condition in each family.ConclusionsThis study corroborates C-terminal CHT truncation as a cause of autosomal dominant dHMN, confirming upper limb predominating over lower limb involvement, and broadening the clinical spectrum arising from CHT malfunction.


Microbiology ◽  
1995 ◽  
Vol 141 (9) ◽  
pp. 2123-2130 ◽  
Author(s):  
F.-X. Berthet ◽  
J. Rauzier ◽  
E. M. Lim ◽  
W. Philipp ◽  
B. Gicquel ◽  
...  

2010 ◽  
Vol 191 (3) ◽  
pp. 645-659 ◽  
Author(s):  
Nadim Maghzal ◽  
Emily Vogt ◽  
Wolfgang Reintsch ◽  
James S. Fraser ◽  
François Fagotto

Epithelial cell adhesion molecule (EpCAM) is best known as a tumor-associated protein highly expressed in carcinomas. The function of this cell surface protein during embryonic development and its potential role in cancer are still poorly understood. We identified EpCAM in a gain-of-function screen for inducers of abnormal tissue mixing during gastrulation. Elevated EpCAM levels in either the ectoderm or the mesoderm confer “invasive” properties to cells in both populations. We found that this phenotype represents an “overstimulation” of an essential activity of EpCAM in controlling cell movements during embryonic development. Surprisingly, this property is independent of the putative adhesive function of EpCAM, and rather relies on a novel signaling function that operates through down-regulation of PKC activity. We show that inhibition of novel PKCs accounts entirely for the invasive phenotype induced by abnormally high levels of EpCAM as well as for its normal function in regulating cell rearrangement during early development.


1986 ◽  
Vol 83 (12) ◽  
pp. 4399-4402 ◽  
Author(s):  
M. Isobe ◽  
K. Huebner ◽  
P. J. Maddon ◽  
D. R. Littman ◽  
R. Axel ◽  
...  

2002 ◽  
Vol 70 (8) ◽  
pp. 4494-4500 ◽  
Author(s):  
Benfang Lei ◽  
Laura M. Smoot ◽  
Heather M. Menning ◽  
Jovanka M. Voyich ◽  
Subbarao V. Kala ◽  
...  

ABSTRACT Analysis of the genome sequence of a serotype M1 group A Streptococcus (GAS) strain identified a gene encoding a previously undescribed putative cell surface protein. The gene was cloned from a serotype M1 strain, and the recombinant protein was overexpressed in Escherichia coli and purified to homogeneity. The purified protein was associated with heme in a 1:1 stoichiometry. This streptococcal heme-associated protein, designated Shp, was produced in vitro by GAS, located on the bacterial cell surface, and accessible to specific antibody raised against the purified recombinant protein. Mice inoculated subcutaneously with GAS and humans with invasive infections and pharyngitis caused by GAS seroconverted to Shp, indicating that Shp was produced in vivo. The blood of mice actively immunized with Shp had significantly higher bactericidal activity than the blood of unimmunized mice. The shp gene was cotranscribed with eight contiguous genes, including homologues of an ABC transporter involved in iron uptake in gram-negative bacteria. Our results indicate that Shp is a novel cell surface heme-associated protein.


2014 ◽  
Vol 38 (1) ◽  
pp. 11-14
Author(s):  
Hassan Hachim Naser

Brucella spp are important food pathogen those can be infected the human-being during consumption of contaminated milk and milk products from sheep, goats, and cattle with Brucella spp. In this study the polymerase chain reaction (PCR) for direct detection of Brucella spp. from milk of sheep and cattle were employed to amplify 233bp product of highly conserved regions of BCSP31 gene encoding a 31-KDa cell surface protein in B. melitensis and B. abortus. The results showed that the sheep were more frequent for shedding of Brucella spp in their milk, where appeared (6/50 samples) at (12%). Whereas the cattle appeared less frequency for shedding of Brucella in their milk, which showed (2/50 samples) at (4%). It can be concluded that PCR technique is highly sensitive and specific technique for direct detection of Brucella from milk and the sheep and cattle can be shedding the Brucella in their milk. Therefore, the contaminated milk with Brucella spp may have dangerous effect on public health, when consumed by human


2005 ◽  
Vol 25 (22) ◽  
pp. 10171-10182 ◽  
Author(s):  
Monica Dentice ◽  
Cristina Luongo ◽  
Antonia Elefante ◽  
Raffaele Ambrosio ◽  
Salvatore Salzano ◽  
...  

ABSTRACT Thyroid transcription factor gene 1 (TTF-1) is a homeobox-containing gene involved in thyroid organogenesis. During early thyroid development, the homeobox gene Nkx-2.5 is expressed in thyroid precursor cells coincident with the appearance of TTF-1. The aim of this study was to investigate the molecular mechanisms underlying thyroid-specific gene expression. We show that the Nkx-2.5 C terminus interacts with the TTF-1 homeodomain and, moreover, that the expression of a dominant-negative Nkx-2.5 isoform (N188K) in thyroid cells reduces TTF-1-driven transcription by titrating TTF-1 away from its target DNA. This process reduced the expression of several thyroid-specific genes, including pendrin and thyroglobulin. Similarly, down-regulation of TTF-1 by RNA interference reduced the expression of both genes, whose promoters are sensitive to and directly associate with TTF-1 in the chromatin context. In conclusion, we demonstrate that pendrin and thyroglobulin are downstream targets in vivo of TTF-1, whose action is a prime factor in controlling thyroid differentiation in vivo.


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