Neuroepithelial cell

Neuroepithelial Cells are progenitor cells in the nervous system, deriving from stem cells in several different stages of development. They appear during embryonic development of the neural tube as well as in adult neurogenesis in specific areas of the central nervous system. These cells have also been called neuroblasts in an effort to delineate them as precursors to neurons and glial cells.

Embryonic neural development

Brain development

During the third week of embryonic growth the brain begins to develop in the early fetus in a process called induction.^[1] Neuroepithelial cells of the ectoderm begin multiplying rapidly and fold in forming the neural plate, which invaginates during the fourth week of embryonic growth and forms the neural tube.^[1] The formation of the neural tube polarizes the neuroepithelial cells by orienting the apical side of the cell to face inward, which later becomes the ventricular zone, and the basal side is oriented outward, which contacts the pial surface.^[2] As part of this polarity, neuroepithelial cell express prominin-1 in the apical plasma membrane as well as tight junctions to maintain the cell polarity.^[3] Integrin α6 anchors the neuroepithelial cells to the basal lamina.^[3] The neural tube begins as a single layer of pseudostratified epithelial cells, but rapid proliferation of neuroepithelial cells creates additional layers and eventually three distinct regions of growth.^[3][1] Further proliferation of the cells in these regions gives rise to three distinct areas of the brain: the forebrain, midbrain, and hindbrain. The neural plate itself eventually gives rise to the spinal cord.^[1]

Neuroepithelial cell proliferation

Neuroepithelial cells are a class of stem cell and have similar characteristics, most notably the ability to self renew. During the formation of the neural tube, neuroepithelial cells undergo symmetric proliferative divisions that give rise to two new neuroepithelial cells.^[3] At a later stage of brain development, neuroepithelial cells begin to self renew and give rise to non-stem cell progenitors such as neurons simultaneously by undergoing asymmetric division.^[3] Expression of Tis21, an antiproliferative gene causes the neuroepithelial cell to make the switch from proliferative division to neuronic division.^[3] Many of the neuroepithelial cells also divide into radial glial cells, a similar, but more fate restricted cell.^[3] During neuroepithelial cell division interkinetic nuclear migration allows the cells to divide unrestricted while maintaining a dense packing.^[3] During G1 the cell nucleus migrates to the basal side of the cell and remains there for S phase and migrates to the apical side for G2.^[3] This migration requires the help of microtubules and actin filaments.^[3]

Radial glial cell switch

Neuroepithelial cells give rise to radial glial cells early on during embryonic development. To make the switch, neuroepithelial cells begin downregulating their epithelial features, particularly the occludin that forms their tight junctions.^[3] Another tight junction protein, PAR3, remains at the apical side of the cell co-localizing with N-cadherin and keeps the apical face of the neuroepithelial cell intact.^[3] In the absence of occludin some polarity is still lost and the neuroepithelial cell gives rise to the radial glial cell.^[3]

Adult Neurogenesis

Genesis of Neuroepithelial Cells in the Adult CNS

In the adult CNS, neuroepithelial cells arise in several different areas of the brain: the subventricular zone (SVZ)and the dentate gyrus of the hippocampus. Often categorized as neural stem cells, neuroepithelial cells give rise to only a few varieties of neural cells, making them multipotential - a definite distinction from the pluripotent stem cells found in embryonic development. Neuroepithelial cells undergo mitosis generating more neuroepithelial cells, radial glial cells or progenitor cells, the latter two differentiating into either neurons or glial cells. The neuroepithelial cells undergo two different forms of mitosis: asymmetric differentiating division and symmetric prolific division.^[3] The asymmetric division results in two different varieties of daughter cells (i.e. a neuroepithelial cell divides into a radial glial cell and another neuroepithelial cell), while the symmetric version yields identical daughter cells. The progenitor cells and radial glial cells respond to extracellular trophic factors - like ciliary neurotrophic factor (CNTF), cytokines or neuregulin 1 (NGR1) - that can determine whether the cells will differentiate into either neurons or glia.^[4]

Neurogenesis in Neural Repair

Neurogenesis in the adult brain is often associated with diseases that deteriorate the CNS, like Huntington's disease, Alzheimer's disease, epilepsy and even Parkinson's disease. While adult neurogenesis is up-regulated in the hippocampus in patients with these diseases, whether its effects are regenerative or inconclusive remains to be seen. ^[5] Neurogenesis is also associated with neuroplasticity in a complementary fashion. The new neurons generated by the neuroepithelial cells, progenitors and radial glial cells will not survive unless they are able to integrate into the system by making connections with new neighbors. This also leads to many controversial concepts, like neurogenic therapy involving the transplant of local progenitor cells to a damaged area.^[6]

Associated Diseases

Oligodendroglial Tumors

Oligodendroglial Tumors manifest in glial cells, which are responsible for supporting and protecting nerve cells in the brain. The tumor develops over olilgodendrocytes and is usually found in the cerebrum around the frontal or temporal lobes. The tumors can either grow slowly in a well-differentiated manner delaying the onset of symptoms, or they can grow rapidly to form an anaplastic oligodendrogliloma. The symptoms for this type of tumor include headaches and visual problems. Additionally, blockage of ventricles could cause build up of cerebral spinal fluid resulting in swelling around the tumor. The location of the tumor may also affect the symptoms since frontal lobe tumors can cause gradual mood or personality changes while temporal lobe tumors result in coordination and speech problems ^[7].

Neuroepithelial Cysts

Neuroepithelial cysts, also known as colloid cysts, develop in individuals between the ages of 20-50 and is relatively rare in individuals under the age of twenty. The cysts are benign tumors that usually appear in the anterior third ventricle. The cysts occur in the epithelium putting their patients at risk for obstructive hydrocephalus, increased intracranial pressure, and rarely intracystic hemorrhage. This results from the cysts enlarging by causing the epithelium to secrete additional mucinous fluid. The cysts are usually found incidentally or if patients become symptomatic presenting with the symptoms of hydrocephalus. The larger cysts are operated on while smaller cysts that are not obstructive can be left alone ^[8].

Dysembryoplastic Neuroepithelial Tumor (DNT)

Dysembryoplastic Neuroepithelial Tumors are a rare, benign tumor that affects children and teenagers under the age of twenty. The tumor occurs in the tissue covering the brain and spinal chord. The symptoms of the tumor are dependent on its location, but most children experience seizures that cannot be controlled by medication. DNT is usually treated through invasive surgery and the long term outlook for patients is generally good ^[9] .

References

1. ^ ^{a b c d} McDonald, Ann (2006). Prenatal Development - The Dana Guide. Dana Press. ISBN 1932594108. http://www.dana.org/news/brainhealth/detail.aspx?id=10050. 
2. ^ Zolessi, Flavio (2009). "Vertebrate Neurogenesis: Cell Polarity". eLS. doi:10.1002/9780470015902.a0000826.pub2. 
3. ^ ^{a b c d e f g h i j k l m n} Götz, Magdalena; Huttner, Wieland (2005). "The Cell Biology of Neurogenesis". Nature 6: 777–788. doi:10.1038/nrm1739. 
4. ^ Clarke, DL (2003). "Stem Cells and Tissue Regeneration: Neural Stem Cells". Bone Marrow Transplantation 32: 13–17. doi:10.1038/sj.bmt.1703937. http://www.nature.com/bmt/journal/v32/n1s/full/1703937a.html. Retrieved 10/26/11. 
5. ^ Taupin, Philippe (5). "Adult neurogenesis, neuroinflammation and therapeutic potential of adult neural stem cells". International Journal of Medical Sciences 5 (3): 127–132. PMC 2424180. PMID 18566676. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2424180. Retrieved 10/26/11. 
6. ^ Taupin, Philippe (5). "Adult neurogenesis, neuroinflammation and therapeutic potential of adult neural stem cells". International Journal of Medical Sciences 5 (3): 127–132. PMC 2424180. PMID 18566676. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2424180. Retrieved 10/26/11. 
7. ^ "Oligodendroglilal Tumors". Macmillan. http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Brain/Typesofbraintumours/Oligodendroglioma.aspx. 
8. ^ Chin, Lawrence S. "Colloid Cysts". Medscape. http://emedicine.medscape.com/article/249401-overview#a04. 
9. ^ "Dysembryoplastic Neuroepithelial Tumor". Children's Hospital Boston. http://www.childrenshospital.org/az/Site812/mainpageS812P0.html. Retrieved 1 Nov 2011. 

External links

• MeSH neuroepithelial+cells