Zebra fish development

Zebra Fish Development during 72 hours:

Ectodysplasin A Gene

      Ectodysplasin A Gene (EDA)

EDA gene: making a protein called ectodysplasin A.

Ectodysplasin A protein: part of a signaling pathway that plays an important role in    interactions between ectoderm and the mesoderm.

Ectoderm-mesoderm interactions are essential for the formation of several structures that  arise from the ectoderm, including the skin, hair, nails, teeth, and sweat glands.

The EDA gene: produce many different versions of ectodysplasin A.

One kind of that is ectodysplasin A1 interacts with a protein called the ectodysplasin A receptor (produced from the EDAR gene). On the cell surface, ectodysplasin A1 attaches to receptor like a key in a lock, and they trigger a series of chemical signals that affect cell activities such as division, growth, and maturation.

Before birth, this signaling pathway controls the formation of ectodermal structures such as hair follicles, sweat glands, and teeth.

Mutations in the EDA gene:  Hypohidrotic ectodermal dysplasia

More than 80 different mutations in the EDA gene have been found. These mutations cause the X-linked form of the disorder, which accounts for 95 percent of all cases of hypohidrotic ectodermal dysplasia.

Some mutations in the EDA gene change single base pairs, while other mutations insert or delete nucleotides in the gene. These changes lead to the production of a nonfunctional version of the ectodysplasin A protein. This abnormal protein cannot trigger chemical signals needed for normal interactions between the ectoderm and the mesoderm. Without these signals, hair follicles, teeth, sweat glands, and other ectodermal structures do not form properly, leading to the characteristic features of hypohidrotic ectodermal dysplasia.

http://www.cell.com/fulltext/S0092-8674(13)00131-1

http://ghr.nlm.nih.gov/gene/EDA

http://en.wikipedia.org/wiki/Ectodysplasin_A2_receptor

   Schwann cells

Schwann cells (SC) named after physiologist Theodor Schwann

: neurolemmocytes that are the principle glia throughout the entire peripheral nervous system (PNS).

The PNS includes all nerves going out to muscles as well as sensory nerves coming from the muscles back to the spinal cord. Schwann cells are a type of “support” cell in the PNS.

There are two types of Schwann cell, myelinating and nonmyelinating. Myelinating Schwann cells wrap around axons of motor and sensory neurons to form the myelin sheath. The sheath is not continuous. Individual myelinating Schwann cells cover about 100 micrometres of an axon—equating to approximately 10,000 Schwann cells along a 1 metre length of the axon—which can be up to a metre or more in length. Myelin is necessary for sending appropriate electrical signals throughout the nervous system.

The gaps between adjacent Schwann cells are called nodes of Ranvier. The vertebrate nervous system relies on the myelin sheath for insulation and as a method of decreasing membrane capacitance in the axon.

 
Schwann cells are not stem cells, they are adult cells and can only be Schwann cells.

Schwann cells are absolutely essential for regeneration in the injured PNS.

Netrin:

Secreted proteins that regulate axon guidance and neuronal migration.

Netrins are genetically conserved across nematode worms, fruit flies, frogs, mice, and humans. 

Netrins are chemotropic; a growing axon will either move towards or away from a higher concentration of netrin

The detailed mechanism is not understood:  netrin attraction is mediated through UNC-40/DCC cell surface receptors and repulsion is mediated through UNC-5 receptors.

 Netrins also act as growth factors, encouraging cell growth activities in target cells. Mice deficient in netrin fail to form the hippocampal commissure or the corpus callosum.

Semaphorin 3

The Semaphorins are the largest family of axon guidance. Semaphorins are divided into 8 classes (classes 3-7 found in vertebrates). Class 3 Semaphorins are secreted.it is a protein that in humans is encoded by the SEMA3A gene.

They are characterized structurally by a conserved 400 amino acid sema domain. 

This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development.

It is secreted by surrounding tissues to guide migrating cells and axons in the developing nervous system of an organism which is critical for the precise formation of neurons and vasculature.

Sema3a repels axons from the dorsal root ganglia, facial nerves, vagal nerves, olfactory-sensory, cortical nerves, hippocampal nerves and cerebellar nerves.

Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines and aberrant release of this protein is associated with the progression of Alzheimer's disease.

http://www.nature.com/nrm/journal/v8/n4/fig_tab/nrm2142_F7.html

http://www.sciencemag.org/site/feature/data/pharmacia/2001/HiramotoF2.xhtml

Anencephaly

Anencephaly

          : Cephalic disorder that is the absence of a major portion of the brain, skull, and scalp.  

             Results from a neural tube defect that occurs when the head end of the neural defect fails to  close, usually between the 23rd and 26th day following conception.

           Anencephaly occurs in about 1 out of every 10,000 births.

         The remaining structure is usually covered only by a thin layer of membrane. Infants with this   disorder do not survive longer than a few hours or possibly days after their birth. A baby born with anencephaly is usually blind, deaf, unaware of its surroundings and unable to feel pain. 

          Neural tube defects do not follow direct patterns. Studies have shown that the addition of folic  acid to the diet of women of child-bearing age may significantly reduce, although not eliminate, the incidence of neural tube defects.

          It is recommended that all women of child-bearing age consume 0.4 mg of folic acid daily.     Physicians may prescribe even higher dosages of folic acid (4 mg/day) for women having had a previous pregnancy with a neural tube defect. 

          Recent animal models indicate a possible association with deficiencies of transcription factor TEAD2.

          It is known that women taking certain medications for epilepsy and women with insulin- dependent diabetes have a higher risk of having a child with a neural tube defect.

         There is no standard treatment for anencephaly and the prognosis for patients is death.

         PITX2

Paired-like homeodomain transcription factor 2 (pituitary homeobox 2) is a protein that in humans is encoded by the PITX2 gene.

: acts as a transcription factor and regulates procollagen lysyl hydroxylase gene expression. Also involved in the development of the eye, tooth and abdominal organs.

Pitx2 is responsible for the establishment of the left-right axis, the asymmetrical development of the heart, lungs, and spleen, twisting of the gut and stomach, as well as the development of the eyes. Once activated Pitx2 will be locally expressed in the left lateral mesoderm, tubular heart, and early gut which leads to the asymmetrical development of organs and looping of the gut. When Pitx2 is deleted, the irregular morphogenesis of organs results on the left hand side.

Nodal

Nodal is a secretory protein that in humans is encoded by the NODAL gene. It is located on chromosome10q22.1. Besides, it belongs to TGF-beta superfamily. It is involved in cell differentiation in early embryogenesis, playing a key role in signal transfer from the node, in the anterior primitive streak, to lateral plate mesoderm (LPM). Nodal signaling is important very early in development for mesoderm and endoderm formation and subsequent organization of left-right axial structures.

Nodal signaling regulates mesoderm formation in a species-specific manner. Thus, in Xenopus, Xnr controls dorsoL-ventral mesoderm formation along the marginal zone. In zebrafish, are responsible for animal-vegetal mesoderm formation. In chicken and mouse, Vg1 and Nodal promote primitive streak formation in the epiblast. In chick development, Nodal is expressed in Koller's sickle.

Sonic hedgehog (shh)

Sonic hedgehog is a protein that in humans is encoded by the SHH gene.

: One of the mammalian signaling pathway family called hedgehog, the others: desert hedgehog (DHH) and Indian hedgehog (IHH).

 SHH plays a key role in regulating vertebrate organogenesis, such as in the growth of digits on limbs and organization of the brain. Sonic hedgehog is the best established example of a morphogen as defined by Lewis Wolpert's French flag model—a molecule that diffuses to form a concentration gradient and has different effects on the cells of the developing embryo depending on its concentration.

SHH in the adult: controls cell division of adult stem cells and has been implicated in the development of some cancers.

SHH is secreted at the zone of polarizing activity, which is located on the posterior side of a limb bud in an embryo.

            The sonic hedgehog transcription pathway has also been linked to the formation of specific kinds of cancerous tumors.

SHH that is expressed in a developing embryo, a related morphogen called Fibroblast growth factors must be secreted from the apical ectodermal ridge. 

http://en.wikipedia.org/wiki/Sonic_hedgehog

http://www.mun.ca/biology/desmid/brian/BIOL3530/DB_03/DBNVert1.html

http://www.cell.com/developmental-cell/abstract/S1534-5807(13)00449-8

Neural Tube Defects and Folate

Neural Tube Defects and Folate

Neural tube defects (NTDs) are one of the severe congenital anomalies that cause by the failure of neurulation. Failure of fusion of the neural tube occurs around the 28th day after conception, when most women do not know they are pregnant.

NTDs in humans is multifactorial disorder; genetic and environmental effects.

Since 1960, scientists suggested that low folate status was important and vital risk factor for NTD. Studies are showed that the folic acid (0.36 mg dosage) supplement reduced the recurrence rate of NTDs from 5.9% to 0.5%. 

Folate is an essential water soluble B vitamin that is particularly from fruits and vegetables.

Neural tube defects (NTD) take place in one out of 1000 in the United States, and they are the second most common type of birth defect after congenital heart defects.

Folate and NTDs

1)     Folates connected to NTD risk through their bioavailability. . Inactivation of the gene FOLR1 coding for folate carrier’s proteins in neuroepithelial, neural crest and visceral endoderm cells cause neural tube defects

2)     Folate is nucleotide synthesis that may be related to NTD risk. The neural tube development require the synthesis of huge amounts of nucleotides in order to facilitate DNA replication due to their rapidly cell dividing.

3)     Adequate functioning of the methylation cycle is important for cranial neural tube closure. 

Refrences:

1)      Imbard A., Benoist j., Blom H. Neural Tube Defects, Folic Acid and Methylation. Int. J. Environ. Res. Public Health 2013, 10, 4352-4389.

2)      Stover, P.J.; Field, M.S. Trafficking of intracellular folates. Adv. Nutr. 2011, 2, 325–331.

3)       Imbard, A.; Smulders, Y.M.; Barto, R.; Smith, D.E.; Kok, R.M.; Jakobs, C.; Blom, H.J. Plasma choline and betaine correlate with serum folate, plasma S-adenosyl-methionine and S-adenosyl-homocysteine in healthy volunteers. Clin. Chem. Lab. Med. 2012, 51, 683–692.

Noggin protein

: Also known as NOG

The NOG gene provides instructions for making a protein called noggin. This protein is involved in the development of many body tissues, including nerve tissue, muscles, and bones. Noggin's role in bone development makes it important for proper joint formation.

Noggin interacts with members of a group of proteins called bone morphogenetic proteins (BMPs). These proteins help control the development of bone and other tissues. In order to begin these developmental processes, BMPs attach (bind) to other proteins called receptors, and this binding stimulates specific cellular processes. The noggin protein regulates the activity of certain BMPs by attaching to them and blocking them from binding to the receptor, which leads to a decrease in BMP signaling.

Tarsal-carpal coalition syndrome: caused by mutations in the NOG gene

Characterized by:  fusion of the individual bones in the wrists (the carpal bones) and in the ankles (the tarsal bones) as well as fusion at the joints between the bones that make up each finger and toe (symphalangism). Symphalangism makes the fingers and toes stiff and difficult to bend.

Bone morphogenetic proteins (BMPs)

A group of growth factors also known as cytokines and as metabologens. Also, a group of pivotal morphogenetic signals, orchestrating tissue architecture throughout the body. They have ability to induce the formation of bone and cartilage.

They have an important role during embryonic development on the embryonic patterning and early skeletal formation. As such, disruption of BMP signaling can affect the body plan of the developing embryo. BMp4 and its inhibitors noggin and chordin help regulate polarity of the embryo. Specifically BMP-4 and its inhibitors play a major role in neurulation and the development of the neural plate. BMP-4 signals ectoderm cells to develop into skin cells, but the secretion of inhibitors by the underlying mesoderm blocks the action of BMP-4 to allow the ectoderm to continue on its normal course of neural cell development.

Chimeras

Chimeras are animals composed of cells that originate from two (or more) different species. In the research lab, chimeras are created by introducing cells from one species into the developing embryo or fetus of another. (The name chimera comes from Greek mythology and describes a creature with the head of a lion, the body of a goat, and the tail of a serpent).

The first chimeras helped scientists understand questions about developmental biology. A sheep-goat chimera, created in 1984, had the head of a goat and the woolly coat of a sheep.

Now, researchers are developing human-animal chimeras to study disease processes, test new drugs, and develop organs for future transplant patients. The chimeras are produced by introducing human stem cells into developing animal embryos.

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Spemann.html

http://ghr.nlm.nih.gov/gene/NOG