User:KMaher123/sandbox

Hello, welcome to my sandbox. Ryan's sandbox is here.

Best source ever: http://books.google.com/books?id=b1-F4NuRXScC&pg=PA703&lpg=PA703&dq=molecular+mechanism+of+medial+hinge+point+cell+folding&source=bl&ots=DcP5b0Sf2r&sig=3USlqXCDbz40pB0uBEwsT80fRR0&hl=en&sa=X&ei=NPBZUerFJKuI0QGI_IHoCw&ved=0CG8Q6AEwBw#v=onepage&q=molecular%20mechanism%20of%20medial%20hinge%20point%20cell%20folding&f=false

Gilbert: pg 339

Disease source:   http://discovery.ucl.ac.uk/82166/          Gerrelli D, Copp AJ. Failure of neural tube closure in the loop-tail (Lp) mutant mouse: analysis of the embryonic mechanism. Dev. Brain Res. 1997;102:217–224.

Convergent extension, planar cell polarity signalling and initiation of mouse neural tube closure Patricia Ybot-Gonzalez,1 Dawn Savery,1 Dianne Gerrelli,1 Massimo Signore, Claire E. Mitchell,2 Clare H. Faux,3 Nicholas D. E. Greene, and Andrew J. Copp4                 http://www.ncbi.nlm.nih.gov.proxy.bc.edu/pmc/articles/PMC1839770/

In mice that exhibit cranio-rachischisis-like symptoms, researchers examined causes for the union failure of the first closure point at the cervial/hindbrain boundary. When the folds were sutured together the folds were able to successfully converge, though they failed to propagate the closure down the remainder of the embryonic axis. This may suggest that the inability of the neural tube to close may come from the inability of the the neural folds to come in proximity eith each other, or in a defect in the actual fusion process.

Many diseases can arise from defects in the neural fold and its derivative tissues.

The transition of the neural plate into the neural tube is primary neurulation. three areas of neural tub closure. Failure to close the posterior neuropore at day 27 results in spina bifida (spinal cord remains exposed). Failure to close the anterior neuropore = lethal condition anencephaly (forebrain remains in contact with the amniotic fluid, and because of that, it deteriorates; skull vault fails to form). In general, the failure of the entire neural tube to close over the entire body axis is called craniorachischisis. Neural tube defects occur 1 in every 1000 live births.

The neural fold is a structure that arises during the process of neurulation in both birds and mammals. Specifically, the neural fold is involved in primary neurulation, and is therefore responsible for the formation of the anterior end of the neural tube in these organisms.

The joining of the neural folds brings about the internalization of the neural crest cells, which give rise to mesenchymal cells, the formation of the neural tube, and the formation of true ectoderm.

The inability of the neural folds to join can result in serious complications for the embryo. In humans,

http://www.embryology.ch/anglais/hdisqueembry/triderm10.html  embryology textbook

http://www.ncbi.nlm.nih.gov/books/NBK10080/ ncbi textbook thing  =) direct quotation follows below

The bending of the neural plate involves the formation of hinge regions where the neural tube contacts surrounding tissues. In these regions, the presumptive epidermal cells adhere to the lateral edges of the neural plate and move them toward the midline (see Figure 12.3B). In birds and mammals, the cells at the midline of the neural plate are called the medial hinge point (MHP) cells. They are derived from the portion of the neural plate just anterior to Hensen's node and from the anterior midline of Hensen's node (Schoenwolf 1991a,b; Catala et al. 1996). The MHP cells become anchored to the notochord beneath them and form a hinge, which forms a furrow at the dorsal midline. The notochord induces the MHP cells to decrease their height and to become wedge-shaped (van Straaten et al. 1988; Smith and Schoenwolf 1989). The cells lateral to the MHP do not undergo such a change (Figures 12.3B,C). Shortly thereafter, two other hinge regions form furrows near the connection of the neural plate with the remainder of the ectoderm. These regions are called the dorsolateral hinge points (DLHPs), and they are anchored to the surface ectoderm of the neural folds. These cells, too, increase their height and become wedge-shaped.

Cell wedging is intimately linked to changes in cell shape. In the DLHPs, microtubules and microfilaments are both involved in these changes. Colchicine, an inhibitor of microtubule polymerization, inhibits the elongation of these cells, while cytochalasin B, an inhibitor of microfilament formation, prevents the apical constriction of these cells, thereby inhibiting wedge formation (Burnside 1973; Karfunkel 1972; Nagele and Lee 1987). After the initial furrowing of the neural plate, the plate bends around these hinge regions. Each hinge acts as a pivot that directs the rotation of the cells around it (Smith and Schoenwolf 1991).

Meanwhile, extrinsic forces are also at work. The surface ectoderm of the chick embryo pushes toward the midline of the embryo, providing another motive force for the bending of the neural plate (see Figure 12.3C; Alvarez and Schoenwolf 1992). This movement of the presumptive epidermis and the anchoring of the neural plate to the underlying mesoderm may also be important for ensuring that the neural tube invaginates into the embryo and not outward. If small pieces of neural plate are isolated from the rest of the embryo (including the mesoderm), they tend to roll inside out (Schoenwolf 1991a). The pushing of the presumptive epidermis toward the center and the furrowing of the neural tube creates the neural folds.

Closure of the neural tube

The neural tube closes as the paired neural folds are brought together at the dorsal midline. The folds adhere to each other, and the cells from the two folds merge. In some species, the cells at this junction form the neural crest cells. In birds, the neural crest cells do not migrate from the dorsal region until after the neural tube has been closed at that site. In mammals, however, the cranial neural crest cells (which form facial and neck structures) migrate while the neural folds are elevating (i.e., prior to neural tube closure), whereas in the spinal cord region, the crest cells wait until closure has occurred (Nichols 1981; Erickson and Weston 1983).

The closure of the neural tube does not occur simultaneously throughout the ectoderm. This is best seen in those vertebrates (such as birds and mammals) whose body axis is elongated prior to neurulation. Figure 12.5 depicts neurulation in a 24-hour chick embryo. Neurulation in the cephalic (head) region is well advanced, while the caudal (tail) region of the embryo is still undergoing gastrulation. Regionalization of the neural tube also occurs as a result of changes in the shape of the tube. In the cephalic end (where the brain will form), the wall of the tube is broad and thick. Here, a series of swellings and constrictions define the various brain compartments. Caudal to the head region, however, the neural tube remains a simple tube that tapers off toward the tail. The two open ends of the neural tube are called the anterior neuropore and the posterior neuropore.

Figure 12.5

Stereogram of a 24-hour chick embryo. Cephalic portions are finishing neurulation while the caudal portions are still undergoing gastrulation. (From Patten 1971; after Huettner 1949.) Unlike neurulation in chicks (in which neural tube closure is initiated at the level of the future midbrain and “zips up” in both directions), neural tube closure in mammals is initiated at several places along the anterior-posterior axis (Golden and Chernoff 1993; Van Allen et al. 1993). Different neural tube defects are caused when various parts of the neural tube fail to close (Figure 12.6). Failure to close the human posterior neural tube regions at day 27 (or the subsequent rupture of the posterior neuropore shortly thereafter) results in a condition called spina bifida, the severity of which depends on how much of the spinal cord remains exposed. Failure to close the anterior neural tube regions results in a lethal condition, anencephaly. Here, the forebrain remains in contact with the amniotic fluid and subsequently degenerates. Fetal forebrain development ceases, and the vault of the skull fails to form. The failure of the entire neural tube to close over the entire body axis is called craniorachischisis. Collectively, neural tube defects are not rare in humans, as they are seen in about 1 in every 500 live births. Neural tube closure defects can often be detected during pregnancy by various physical and chemical tests.

Figure 12.6

Neurulation in the human embryo. (A) Dorsal and transverse sections of a 22-day human embryo initiating neurulation. Both anterior and posterior neuropores are open to the amniotic fluid. (B) Dorsal view of a neurulating human embryo a day later. The (more...) Human neural tube closure requires a complex interplay between genetic and environmental factors. Certain genes, such as Pax3, sonic hedgehog, and openbrain, are essential for the formation of the mammalian neural tube, but dietary factors, such as cholesterol and folic acid, also appear to be critical. It has been estimated that 50% of human neural tube defects could be prevented by a pregnant woman's taking supplemental folic acid (vitamin B12), and the U.S. Public Health Service recommends that all women of childbearing age take 0.4 mg of folate daily to reduce the risk of neural tube defects during pregnancy (Milunsky et al. 1989; Czeizel and Dudas 1992; Centers for Disease Control 1992).

The neural tube eventually forms a closed cylinder that separates from the surface ectoderm. This separation is thought to be mediated by the expression of different cell adhesion molecules. Although the cells that will become the neural tube originally express E-cadherin, they stop producing this protein as the neural tube forms, and instead synthesize N-cadherin and N-CAM (Figure 12.7). As a result, the surface ectoderm and neural tube tissues no longer adhere to each other. If the surface ectoderm is experimentally made to express N-cadherin (by injecting N-cadherin mRNA into one cell of a 2-cell Xenopus embryo), the separation of the neural tube from the presumptive epidermis is dramatically impeded (Detrick et al. 1990; Fujimori et al. 1990).

Figure 12.7

Expression of N-cadherin and E-cadherin adhesion proteins during neurulation in Xenopus. (A) Normal development. In the neural plate stage, N-cadherin is seen in the neural plate, while E-cadherin is seen on the presumptive epidermis. Eventually, the (more...)   "