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Part 1c

EPIDERMAL DEVELOPMENT
Exact transcription of Brons slide:

In embryo, stem cells differentiate into stem cells or epidemal layers by:
- Environmental conditions such as matrix changes due to injury - OR -
-prior cell assymmetry
Cells lose CAM (integrins) and migrate away from basal lamina; develop other CAM during formation of more surface layers
Proliferation of layers and keratinization controlled by TGF-a, FGF and other growth hormones.

What the HECK does he mean by all this? His lecture was unintelligible and so are his slides.

OK, I can tell from the illus that an assymetrical cell can divide and have different parts in the two cells that come from the one, causing them to differentiate differently. So that's the prior cell assymmetry option. I suppose the environmental conditions that could cause the stem cell to finally reach terminal differentiation might be an epidermal cell getting close enough to the surface, or being exposed by a cut. Which is why if you cut or burn yourself all the way through the epidermal layer it is so much slower to heal---because there are no cells there that are determined to become skin cells, so you get scarring of the subdermal layers instead. I think I understand it.

Next page, wound healing.

thrombus = a blood clot, the final product of the blood coagulation step in hemostasis. It is achieved via the aggregation of platelets that form a platelet plug, and the activation of the humoral coagulation system (i.e. clotting factors). A thrombus is physiologic in cases of injury, but pathologic in case of thrombosis. A thrombus is a blood clot in an intact blood vessel. A thrombus in a large blood vessel will decrease blood flow through that vessel. In a small blood vessel, blood flow may be completely cut-off resulting in death of tissue supplied by that vessel. If a thrombus dislodges and becomes free-floating, it is an embolus.

platelet plug = platelets adhere to each other via adhesion receptors or integrins, and to the endothelial cells in the wall of the blood vessel forming a haemostatic plug in conjunction with fibrin.

neutrophil = the most abundant type of white blood cells and form an integral part of the immune system. Their name arrives from staining characteristics on hematoxylin and eosin (H&E) histological preparations. Whereas basophilic cellular components stain dark blue and eosinophilic components stain bright red, neutrophilic components stain a neutral pink. These phagocytes are normally found in the blood stream.

transit amplifying cells = ? Direct Brons quote "Differentiation of stem cells and 'transit amplifying cells' into by TGF-beta in dermis, causes an increase in actin & other contractile proteins to pull tissue edges together".

My notes: fibroblast plus TGF becomes myofibroblast, so it can make actin and myosin and repair muscle

ON WITH THE EMBRYO: WEEK 1
-Fertilization in the ampulla of the uterine tube
-Cleavage = repeated mitosis of fertilized egg (zygote) during migration to uterus
-Morula stage = cluster of cells linked by CAM (cell adhesion molecules)
-Blastocyst: differentiation --- becomes hollow when sodium and water are secreted into morula via Na+/K+ ATP-ase (sodium potassium pump). Inner cell mass (128 cells?) inside blastula becomes embryo, trophoblast surface becomes placenta.
-blastula implantws in uterine endometrium
-now called trophoblast (outside sphere that will be placenta) and embryoblast (inner cell mass).

blastula = an early stage of embryonic development in animals. It is also called blastosphere. It is produced by cleavage of a fertilized ovum and consists of a spherical layer of around 128 cells surrounding a central fluid-filled cavity called the blastocoel. The blastula follows the morula and precedes the gastrula in the developmental sequence.

ectopic pregnancy = 95=97% implantation occurs in tube, others include abdominal and ovarian.

WEEK 2
-Inner cell mass divides into two epithelial layers that form spaces, the epiblast and hypoblast. The epiblast cavitates to form amniotic cavity and produces the majority of the embryonic cells in a saucer shape. The hypoblast stretches to a larger sphere and fuses to form the yolk sac. The yolk sac deivides and only the secondary sac remains. The trophoblast will form placenta. The hypoblast secretes signaling factors for early induction of head and heart formation.

WEEK 3
Gastrulation is the formation of the three germ layers from the epiblast: ectoderm, mesoderm and endoderm. The primitive streak runs from the primitive node (Organizer) to the edge of the saucer, and it generates mesenchyme, TFs and signaling factors. Epiblast cells transform into bottle cells, loose their CAM, erode from the primitive streak, migrate to below the epiblast, and differentiate into mesoderm and endoderm. The remaining epiblast become ectoderm.

The formation of the mesoderm involves the conversion of epithelial to mesenchymal cells. Primitive node and streak cells secrete bone morphogenetic protein (BMP) & nodal, both members of the TGF family, to induce cell differentiation. Primary mesenchymal cells can move! They re-aggregate into secondary epithelium (below epiblast). Secondary epithelium either remains epithelium or differentiates into various types of CT via EMT (epitheliai-mesenchyme transition).

PATHOLOGY: In adult stage secondary epithelia can transform into tumors that undergo EMT to metastasize. Also, rental tubules can change from epithelium into CT to generate fibrosis of the kidney.

1d: POST GASTRULATION

allantoic = gut

Epiblast becomes ectoderm and primitive streak. Ectoderm becomes nervous system and skin. Primitive streak becomes mesoderm, endoderm and notochordal process. Endoderm becomes gut organs.

GERM CELL DERIVATIVES

ECTODERM -- CNS, brain and spinal cord, glia, sensory epithelium of the eye and nose. Neural crest becomes PNS, sensory/autonomic ganglia, Scwann cells, pia, arachnoid, adrenall medulla! Also becomes dermal pigmented cells and bone & CT of face and neck. Also epidermis, hair, nails, teeth enamel, surface glands (mammary, pituitary). Not sure how pituitary is surface....

MESODERM -- becomes CT: bone, cartilate, CT, blood, muscle (all 3 kinds), glands (kidney, gonads, spleen, adrenal cortex), pleura, pericardium, peritoneum, various bursae.

ENDODERM --- epithelium of gut tube, GI, respiratory system, bladder/urethra, tympanic cavity/auditory tubes, tonsils, thyroid, parathyroid, liver, pancreas, thymus.

SONIC HEDGEHOG = Shh = a notochord signaling molecule that induces differentiation and formation of the neural tube by activating TFs.

notochord = becomes the spine!! a flexible, rod-shaped body found in embryos of all chordates. It is composed of cells derived from the mesoderm and defines the primitive axis of the embryo. In lower vertebrates, it persists throughout life as the main axial support of the body, while in higher vertebrates it is replaced by the vertebral column. The notochord is found on the ventral surface of the neural tube.
Notochords were the first "backbones", as well, serving as support structures in chordates that lacked a bony skeleton. The very first vertebrates, such as Haikouicthys, had only a notochord. This is the reason the embryos of vertebrates have them today; embryonic evolution often happens to follow a pattern similar to the ancestral development of the modern animal's traits. Notochords were advantageous to primitive fish-ancestors because they were a rigid structure for muscle attachment, yet flexible enough to allow more movement than, for example, the exoskeleton of the dominant animals of that time. In humans, they eventually develop into the disks between the vertebrae.

nerulation = ectoderm rolls up into a tube, cylinder formation (fundamental form of morphogenesis). Neural tube created by fusion of neural folds bordering the neural groove. Neural tube separates from the ectodermal layers to form the CNS.

Neural crest cells remain separate. Tips of tube migrate away, migrate into mesoderm to form PNS incl sensory neurons and glia. ANS (autonomic nervous system) postganglionic cells including adrenal medulla and enteric nervous system in gut. Also becomes melanocytes in skin.

glia = ganglia = clusters of cell bodies in autonomic nervous system, sympathetic, ???

mechanics of nerulation = adhesion belt of adherens junctions overlie band of actin molecules that contract with mysoin to invaginate epithelial sheet. Contraction of adhesion belt narrows cell apices cuasing sheet to roll up and pinch off.

somites = little segments on outside of neural tube that become vertebrae, called primitive segments in older texts. = masses of mesoderm distributed along the two sides of the neural tube and that will eventually become dermis (dermatome), skeletal muscle (myotome), and vertebrae (sclerotome). They originate from paraxial mesoderm which, towards the end of the third gestational week, becomes organized into loose masses of cells called somitomeres. Driven by changes in the expression of adhesion molecules, somitomeres compact and bud off to form the somites. Approximately 44 somites form and give rise to the bones of the face, vertebral column, associated muscles, and overlying dermis.

WEEK 4

Folding of the embryo--flat disc becomes closed cylinder forming gut tube. Amniotic cavity enlarges and bends embryo ventally into a cylinder, (head and tail ends curl under), most of yolk sac pulls away, hollows inside are coelom which becomes three bursae around organs (pleura, pericardium and peritoneum). Coelom has notochord and somites. Horseshoe shaped space within edge of embryonic mesoderm is made from partial incorporation of yolk sac and is the future gut tube with oral and anal ends established

CHART OF TERATOGEN SUSCEPTIBILITY: Embryo is very sensitive to teratogens until week 8 or so--the change from being considered an embryo to being a fetus is determined by this. After week 8 or so the heart, and limbs are mostly set up, the brain can still get botched as can the ears, eyes, teeth, palate and external genitalia.

teratogen = from the Greek for MONSTER = seems to mean anything that can cause a birth defect... Currently, its most instrumental meaning is that of the medical study of teratogenesis, congenital malformations or grossly deformed individuals. Monster is a pejorative term for a grossly deformed individual, although it is interesting to note that, etymologically, this word is related to demonstration, and used to simply mean something worth looking at, for being unusual, without necessarily being pejorative. Another term for this is dysmorphology, which literally means "the study of abnormal form." Birth defects are known to occur in 3-5% of all newborns. They are the leading cause of infant mortality in the United States, accounting for more than 20% of all infant deaths. Seven to ten percent of all children will require extensive medical care to diagnose or treat a birth defect. Although significant progress has been made in identifying etiologic causes of some birth defects, approximately 65% have no identifed cause.

A wikipedia list of teratogenic birth defects:
Ionizing radiation: atomic weapons, radioiodine, radiation therapy
Infections: cytomegalovirus, herpes virus, parvovirus B-19, rubella virus (German measles), syphilis, toxoplasmosis, Venezuelan equine encephalitis virus
Metabolic imbalance: alcoholism, endemic cretinism, diabetes, folic acid deficiency, hyperthermia, phenylketonuria, rheumatic disease and congenital heart block, virilizing tumors
Drugs and environmental chemicals: 13-cis-retinoic acid, isotretinoin (Accutane), aminopterin, androgenic hormones, busulfan, captopril, enalapril, chlorobiphenyls (PCBs), Dioxin, coumarin, cyclophosphamide, diethylstilbestrol, diphenylhydantoin (Phenytoin, Dilantin, Epanutin), ethanol, ethidium bromide, etretinate, lithium, methimazole, organic mercury, penicillamine, tetracyclines, thalidomide, trimethadione, uranium, methoxyethyl ethers and valproic acid.

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