XML Feed for RxPG News   Add RxPG News Headlines to My Yahoo!   Javascript Syndication for RxPG News

Research Health World General
 
  Home
 
 Latest Research
 Cancer
 Psychiatry
 Genetics
 Surgery
 Aging
 Ophthalmology
 Gynaecology
 Neurosciences
 Pharmacology
 Cardiology
 Obstetrics
 Infectious Diseases
 Respiratory Medicine
 Pathology
 Endocrinology
 Immunology
 Nephrology
 Gastroenterology
 Biotechnology
 Radiology
 Dermatology
 Microbiology
 Haematology
 Dental
 ENT
 Environment
 Embryology
 Orthopedics
 Metabolism
 Anaethesia
 Paediatrics
 Public Health
 Urology
 Musculoskeletal
 Clinical Trials
 Physiology
 Biochemistry
 Cytology
 Traumatology
 Rheumatology
 
 Medical News
 Health
 Opinion
 Healthcare
 Professionals
 Launch
 Awards & Prizes
 
 Careers
 Medical
 Nursing
 Dental
 
 Special Topics
 Euthanasia
 Ethics
 Evolution
 Odd Medical News
 Feature
 
 World News
 Tsunami
 Epidemics
 Climate
 Business
Search

Last Updated: Sep 13th, 2006 - 09:53:57

Cytology Channel
subscribe to Cytology newsletter

Latest Research : Cytology

   DISCUSS   |   EMAIL   |   PRINT
Disrupted Intercellular Communication Causes a Disfiguring Birth Defect
Sep 13, 2006, 09:50, Reviewed by: Dr. Priya Saxena

The researchers propose that gap junction communication is inhibited by interactions between Eph-positive and ephrin-positive cells that cause Cx43 to be sequestered inside cells, where they can’t form gap junction pores and establish cell-to-cell communication—leading to skeletal abnormalities.

 
Before a fertilized egg begins the repeated rounds of cell division that turn the single cell into a proliferating, streaming, differentiating mass of cells, its fate may already be sealed. Inherited mutations in genes involved in segregating and sorting embryonic cells can result in serious abnormalities in body patterning and appear to underlie an inherited X-linked disorder (so-called because the mutated genes lie on the X chromosome) called craniofrontonasal syndrome (CFNS). X-linked disorders tend to affect males more severely than females, because boys inherit just one X chromosome while girls inherit two: if one gene is defective, the other can fill in. CFNS is a rare departure from this pattern, with females exhibiting the most severe symptoms. This disfiguring disorder is characterized by a range of skull aberrations, including facial asymmetry, widely spaced eyes, and abnormal head shape, as well as polydactyly and fused digits.

A class of receptor protein-tyrosine kinases called Ephs and their ephrin binding partners (called ligands) regulate tissue patterning by restricting cell interactions, ensuring proper cell sorting, and establishing developmental compartment boundaries. Mutations in one ephrin gene, ephrin-B1, have been identified in patients with CFNS and have been associated with aberrant skeletal patterning in mutant “heterozygous” female mice, which carry one normal and one nonfunctional copy of the ephrin-B1 gene. Mutations in connexins, structural proteins that form gap junction pores, also lead to cranial and skeletal defects in both mice and humans.

Localization of ephrin-B1 (green) and connexin43 (red) in 3T3 cells.

In a new study, Alice Davy, Jeffrey Bush, and Philippe Soriano elucidate the mechanisms of ephrin-mediated cell sorting, and show how the breakdown of the process causes physical abnormalities. The researchers worked with ephrin-B1 heterozygous female mice, polydactyl mutants with abnormally developed frontal bones in the skull (called the calvarial phenotype, after the name of the bones). They show that Eph/ephrin signaling regulates gap junction communication, which in turn controls cell sorting. Their results indicate that flawed cell sorting, resulting from dysregulated communication at gap junctions—intracellular membrane channels with pores that allow coupled cells to exchange small molecules—underlies the skeletal abnormalities observed in the mice.

Previous studies established that ephrin-B1 heterozygous females exhibit polydactyly while males lacking their copy of ephrin-B1 and females lacking both copies do not. Polydactyly accompanied a random inactivation of X chromosomes in female cells (in which one X chromosome is silenced in some cells and the second is silenced in others) that created a mosaic pattern of ephrin-B1 expression, with ephrin-B1-expressing cells segregated from cells that didn’t express the gene. Ephrin-B1 mutants also develop multiple defects in tissue derived from neural crest cells—which give rise to cartilage, bone, connective tissue, and other specialized tissues.

In this study, Davy et al. show that the mosaic loss of ephrin-B1 blocked the differentiation of neural crest cells by disrupting the distribution of a connexin (Cx43) that regulates bone cell differentiation and forms gap junctional pores. Cx43 aggregated between wild-type (nonmutant) cells and between cells that lack ephrin-B1, but was rarely seen at the border between ephrin-B1-positive and -negative cells, suggesting that the mosaic cells restricted the number of junctional pores. Expression of the ephrin-B1 receptor, EphB2, is elevated in ephrin-B1-negative regions in ephrin-B1 heterozygous embryos, so the researchers suspected that interactions between the receptor and ligand reduced Cx43 levels and disrupted gap junction formation—which they confirmed by tracking gap junction communication in cell cultures. This defect might be mediated by a physical interaction between ephrin-B1 and Cx43.

The researchers propose that gap junction communication is inhibited by interactions between Eph-positive and ephrin-positive cells that cause Cx43 to be sequestered inside cells, where they can’t form gap junction pores and establish cell-to-cell communication—leading to skeletal abnormalities. This explains why the CFNS phenotype is more prevalent in females (who exhibit mosaic expression of ephrin-B1 through X inactivation). By contributing a mouse model with skull and digit defects that mimic those seen in humans, the researchers have provided a valuable platform for future investigations into the role of ephrins and gap junction communication in disfiguring skeletal disorders.
 

- Gross L (2006) Disrupted Intercellular Communication Causes a Disfiguring Birth Defect. PLoS Biol 4(10): e335
 

Read Research Article at PLoS Biology Website

 
Subscribe to Cytology Newsletter
E-mail Address:

 

Written by Liza Gross

Published: September 12, 2006

DOI: 10.1371/journal.pbio.0040335

Copyright: © 2006 Public Library of Science. This is an open-access article distributed under the terms of the Creative Commons Attribution License


Related Cytology News

How cells adhere so firmly to blood vessel walls
New Insight into Cell Division
New method for the controlled initiation of membrane fusion
CPK3 and CPK6 function as ion channel regulators in guard cell signaling
Disrupted Intercellular Communication Causes a Disfiguring Birth Defect
Sharing Responsibility for Clathrin Coat Assembly
Understanding the process of AIF release following MOMP during apoptosis
Researchers discover new cell structures
Cilia also contribute to cellular response to external signals
A riboswitch might sense magnesium levels in the cell


For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 

© Copyright 2004 onwards by RxPG Medical Solutions Private Limited
Contact Us