Welcome to The Visible Embryo
  o
 
The Visible Embryo Home
   
Google  
Home--- -History-----Bibliography-----Pregnancy Timeline-----Prescription Drugs in Pregnancy---- Pregnancy Calculator----Female Reproductive System----News----Contact
 
WHO International Clinical Trials Registry Platform


The World Health Organization (WHO) has a Web site to help researchers, doctors and patients obtain information on clinical trials. Now you can search all such registers to identify clinical trial research around the world!





Home

History

Bibliography

Pregnancy Timeline

Prescription Drug Effects on Pregnancy

Pregnancy Calculator

Female Reproductive System

News

Disclaimer: The Visible Embryo web site is provided for your general information only. The information contained on this site should not be treated as a substitute for medical, legal or other professional advice. Neither is The Visible Embryo responsible or liable for the contents of any websites of third parties which are listed on this site.


Content protected under a Creative Commons License.
No dirivative works may be made or used for commercial purposes.

 

Pregnancy Timeline by SemestersDevelopmental TimelineFertilizationFirst TrimesterSecond TrimesterThird TrimesterFirst Thin Layer of Skin AppearsEnd of Embryonic PeriodEnd of Embryonic PeriodFemale Reproductive SystemBeginning Cerebral HemispheresA Four Chambered HeartFirst Detectable Brain WavesThe Appearance of SomitesBasic Brain Structure in PlaceHeartbeat can be detectedHeartbeat can be detectedFinger and toe prints appearFinger and toe prints appearFetal sexual organs visibleBrown fat surrounds lymphatic systemBone marrow starts making blood cellsBone marrow starts making blood cellsInner Ear Bones HardenSensory brain waves begin to activateSensory brain waves begin to activateFetal liver is producing blood cellsBrain convolutions beginBrain convolutions beginImmune system beginningWhite fat begins to be madeHead may position into pelvisWhite fat begins to be madePeriod of rapid brain growthFull TermHead may position into pelvisImmune system beginningLungs begin to produce surfactant
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development




 

Loss of essential protein linked to hydrocephalus

Researchers at St. Jude Children's Research Hospital have developed mice lacking the Alix protein, in order to study hydrocephalus or "water on the brain." Alix orients epithelial cells in the brain's choroid plexus in order to prevent compromises to the brain's barrier layer.


St. Jude Children's researchers then painstakingly examined the Alix protein and how it promotes the correct assembly and position of connections between epithelial cells called tight junctions.

By interacting with the actin cytoskeleton — the microscopic network of protein filaments and tubes within cytoplasm, Alix forms the actomyosin-tight junction complex, laying cells in a specific pattern and forming a "molecular bridge." Alix determines the polarity of individual epithelial cells and then orients them in relation to one another throughout the epithelial cell layer.

The research appears in the journal Nature Communications.


"Our study unravels the central role Alix plays — not only in preserving the general architecture of the epithelium and the epithelial barrier, but also in how this protein contributes to the maintenance of brain homeostasis [or equilibrium].

"We found the loss of Alix causes striking defects in actomyosin assembly and tight junction formation. These changes are so fundamental, they lead to prominent alterations in cell shape and loss of cell polarity — ultimately affecting the epithelial barrier."

Alessandra d'Azzo PhD, holder of the Jewelers For Children Endowed Chair in Genetics and Gene Therapy, St. Jude Children's Research Hospital.


Located in the choroid plexus of the brain, the epithelial barrier produces the cerebrospinal fluid (CSF) in brain ventricles. Crucial in balancing the movement of ions, molecules and other metabolites, CSF also acts as a protective barrier against mechanical damage and disease. However, excess CSF fluid accumulation can lead to hydrocephalus.

It was through analysis of high-resolution images that the team observed loss of Alix protein led to an increased discharge of epithelial cells — a process called "cell extrusion." Extrusion is when a new cell replaces an existing one by "pushing up" and discarding the damaged one from the epithelial layer. "It is an important physiological mechanism for the ordered removal of cells from the epithelial layer, but when it is out of control — has profoundly damaging effects," explained Yvan Campos PhD, associate scientist in the St. Jude Department of Genetics, and the paper's first author.


Unrestrained epithelial cell extrusion has been linked to tumor cell invasion and metastasis in other studies.


Looking ahead, the newly generated mouse model offers an opportunity to study hydrocephalus on a molecular level. Although hydrocephally is a fairly common clinical condition in humans, its causes are still unexplained. Researchers also hope that this new mouse model will help explain the role of Alix protein in cancers.

Abstract
Maintenance of epithelial cell polarity and epithelial barrier relies on the spatial organization of the actin cytoskeleton and proper positioning/assembly of intercellular junctions. However, how these processes are regulated is poorly understood. Here we reveal a key role for the multifunctional protein Alix in both processes. In a knockout mouse model of Alix, we identified overt structural changes in the epithelium of the choroid plexus and in the ependyma, such as asymmetrical cell shape and size, misplacement and abnormal beating of cilia, blebbing of the microvilli. These defects culminate in excessive cell extrusion, enlargement of the lateral ventricles and hydrocephalus. Mechanistically, we find that by interacting with F-actin, the Par complex and ZO-1, Alix ensures the formation and maintenance of the apically restricted actomyosin–tight junction complex. We propose that in this capacity Alix plays a role in the establishment of apical–basal polarity and in the maintenance of the epithelial barrier.

The paper's other authors are Xiaohui Qiu, Elida Gomero, Randall Wakefield, Linda Horner, Young-Goo Han, David Solecki and Sharon Frase, all of St. Jude; Wojciech Brutkowski of the Polish Academy of Sciences; and Antonella Bongiovanni of the Institute of Biomedicine and Molecular Immunology, National Research Council.

The study was funded by the National Institutes of Health (grants AR049867, GM60905, GM104981 and DK52025), the Assisi Foundation of Memphis, and ALSAC.

St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20 percent to 80 percent since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food -- because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude on Twitter and Instagram at @stjuderesearch.
Return to top of page

Jun 24, 2016   Fetal Timeline   Maternal Timeline   News   News Archive   



Loss of Alix protein results in the defective orientation of cilia (RIGHT) on the ependyma —
the protective epithelial barrier which exists between the brain and cerebrospinal fluid.
Image Credit: St. Jude Children's Research Hospital


 


 

Phospholid by Wikipedia