Monday, June 16, 2014

Embryology


Zygote: fertilized egg (1 cell), divides through mitosis

Embryogenesis: stages of development between fertilization and birth

Processes of embryogenesis:

·         Fertilization: fusion of the gametes

·         Cleavage: series of mitotic cell divisions after fertilization. The cytoplasm forms many small cells, called blastomeres, which form a sphere (blastula)

·         Gastrulation: Blastomeres change their relative positions; the three germ layers of the embryo form (endoderm, mesoderm, ectoderm)

·         Organogenesis: Cells interact with one another and rearrange themselves to produce tissues and organs

·         Metamorphosis: in some animals, larva become sexually mature adult organisms

·         Gametogenesis: germ cell differentiation occurs


       Epigenesis: the view that organs of an embryo are formed de novo (from scratch) each generation

        Preformation: the view that organs are already present, in miniature form, within an egg and a sperm.

     The Preformation theory is flawed n that it is unable to account for intergenerational genetic variations

Now, most biologists believe that instructions for the formation of the organism are present in a fertilized egg

    Primary germ layers and early organs
        Pander discovered germ layers: ectoderm, mesoderm and endoderm


      Ectoderm: outer layer of embryo, produces epidermis, brain and nervous system
      Mesoderm: generates blood, connective tissue, heart, kidneys, gonads, bones and muscles
     Endoderm: inner layer of embryo, forms epithelium of digestive tube and associated organs


   The four principles of Karl Ernat Von Baer
        1. The general features of a large group of animals appear earlier in development than do the specialized features of a smaller group

     2. Less general characteristics develop from the more general until finally the most specialized appear

       3. An embryo does not pass through the state/formations of other organisms but instead separates itself from them
5    
        4. The embryo of a higher form never resembles an adult of another form, but only an embryo of its own form 



     Blastospore: dimple, marks fixture dorsal (top) side of embryo. Formed at the beginning of gastrulation.

    The blastospore expands to form a ring. Cells that migrate through it become mesoderm
   The endoderm cells are the large yolky cells in the vegetal hemisphere.

   Notochord: rod of mesodermal cells in the most dorsal portion of the embryo. Signals ectodermal cells above it to form a tube and become the nervous system instead of forming the epidermis

    Neural precursor cells elongate, stretch and fold into the embryo, forming the neural tube
    Mesodermal cells near the neural tube and notochord are segmented into somites

    Somites: precursors to the back, skeleton and spine 


      Sources: "Developmental Biology" Tenth Edition - Scott F Gilbert




Stem Cells and Cancer: Cause

It is so far unclear to what extent cancer might be caused by the unchecked replication of mutated stem cells. Cancer stem cells (CSCs) are undifferentiated and replicate indefinitely. some scientists believe these cells arise from mutated stem cells, while others believe them to be the result of mutated progenitors or differentiated cells that have become de-differentiated. Because stem cells can self-renew, their life spans are longer than those of mature differentiated cells. This makes it more likely that CSCs arise from stem cells, as it would take a long time for specialized adult cells to mutate in all the ways necessary for them to obtain the characteristics of cancer cells. Having a long enough lifespan to undergo the mutations needed to form tumors and undergo metastasis would be rare for a differentiated cell. Sox 2, an important factor in maintaining the pluripotent, undifferentiated state of stem cells, has been linked with the proliferation of cancer cells, and some treatments attempt to target sox 2.

Dear stem cell

If you can be anything,
Be my grandfather's brain
Be words he hasn't spoken
In 600 days
And memories of when
He sang in the car with my mother
To show tunes and even now she says
It was her happiest moment
And when it's quiet she whispers
"I wish my dad was really here"

If you can be anything, be
My best friend's lungs
My mother's eyes-
She says they are going
She says she's afraid
She says nothing but I know
She needs you

If you can be anything,
Be
Everything

Stem cells and Musashi

Musashi is a family of RNA- binding proteins that are expressed in the nervous system. Musashi (Msi) proteins are fundamental in progenitor cells. Musashi 1 is a known marker or neural stem cells in humans, and plays an important role in differentiation and in maintaining the stem cell state. Msi1 has also been seen in intestinal epithelial cells, whose stem cells are not well known or understood by scientists. The musashi gene also helps regulate the asymmetric division of sensory organ precursor cells (SOPs). Musashi helps regulate gene expression and translation; it inhibits the translation of the TTK69 protein in certain neural precursor cells. Experiments have shown that the overexpression of Msi1 will lead to proliferation of stem cells, indicating that the protein plays an important role in maintaining and regulating stem cells, as well as serving as a marker by which scientists can identify and isolate neural progenitor cells and stem cells. Msi1 has been observed mainly in the periventricular ependymal cells and astrocytes. These cells are significant in that they maintain a stem cell state while in the adult brain. There is another musashi protein, musashi 2, that appears to have similar functions to those performed by musashi1. Musashi' role in regulating the translation of specific mRNA could be vastly important to our understanding of the nervous system and of stem cells. 


Source: http://www.sciencedirect.com.proxy.library.georgetown.edu/science/article/pii/S001448270500090X

Stem cell niches

Some adult tissues contain stem cells that are continuously regenerating (epidermis, hair follicles, blood cells, sperm cells, etc.), while others do not (nervous system, skeletal muscle). Stem cells produce daughter cells that can be differentiated or remain stem cells. Stem cell niches house continuously proliferating stem cells. They allow for regulated self-renewal of the stem cells and differentiation of those that leave the niche. Bone marrow is a stem cell niche, as are the placenta, the heart, the testes and the umbilical cord. The HSC niche produces many types of blood cells and is located in bone marrow. The HSC niche is able to regulate the production of blood cells, when one is at high altitudes, more red blood cells will be produced, and during an infection more white blood cells will be produced.

Sources: "Developmental Biology" Tenth Edition - Scott F. Gilbert

Stem cell factor (SCF)

SCF supports cell survival, proliferation and differentiation. It acts on many types of cells, including but not limited to stem and progenitor cells.

Stem cell factor is a paracrine factor. It activates MITF (microphthalmia- associated transcription factor), which plays a role in melanocyte and osteoclast development by binding to the receptor tyrosine kinase Kit. The absence of SCF leads to an absence of the Kit protein, which in turn can cause genetic heterogeneity- the creation of similar phenotypes from mutations in various genes (ex. anemia, albinism, sterility). SCF is produced by dermal cells. When Kit binds to SCF, it is able to prevent apoptosis and increase cell division of melanoblast precursors. Without Kit and SCF, neural crest cells would not replicate enough to sufficiently cover the skin. SCF is also needed for the survival and movement of primordial germ cells. It has yet another important function in regulating hematopoietic stem cells (HSCs) in the bone marrow. Without SCF, HSCs, which are undifferentiated and pluripotent stem cells, will die.



Vocabulary:
Melanocyte: specialized skin cell with the melanin pigment

Osteoclast: bone cell with multiple nuclei; helps with the absorption and dissolution of bone

Paracrine: denotes the secretion and binding of a hormone from one organ to another

Transcription factor: a protein that binds to a specific sequence of DNA, regulating the transcription of DNA into mRNA

Apoptosis: programmed cell death

Melanoblast: precursor of a melanocyte, originates in the neural crest

Neural crest: a group of embryonic cells that are not part of the CNS but migrate to and help form many parts of the nervous system

Sources: "Developmental Biology" Tenth edition - Scott F. Gilbert

Saturday, June 14, 2014

Stem cell therapy

It has been discovered that the pluripotent stem cells found in embryos can migrate from a fetus to the blood of the pregnant mother. Once there, these stem cells can integrate into the mother's organs and help any diseased or damaged organs. This provides evidence of the potential benefits of embryonic/pluripotent stem cells in medicine. Stem cells could be used to regenerate damaged organs and could even work to combat the effects of aging on the body. Stem cells' undifferentiated and regenerative nature makes them potentially useful in treating diseases including Parkinson's, Alzheimer's, diabetes and cirrhosis, all of which involve the degeneration of adult cells.

While embryonic stem cells are the most useful for treatments, there are issues with using them in medical applications. Since they are not derived from the patient him or herself, they have a distinct genotype and could be rejected by the immune system of the patient. Also, the use of embryonic stem cells presents an ethical dilemma. Scientists have attempted to solve both of these problems with induced pluripotent stem cells, somatic cells that are given pluripotency. It is possible to create these cells because the differentiated state of adult cells must be maintained by transcription factors; in the absence of these factors, a cell will return to an undifferentiated state. IPS cells can be created by adding activated genes including sox 2 and oct4, which inhibit differentiation and support pluripotency. The success of IPS cells was shown in an experiment done on mice in which the IPS cells helped treat sickle-cell anemia.

Sources: "Developmental Biology" Tenth Edition- Scott F Gilbert