Devel. bio exam 3 sg cards.txt

  1. What is angiogenesis?
    The remodeling of primary capillary networks that creates veins and arteries. This requires capillary network.
  2. What are tip cells?
    Epithelial cells that respond to VEGFA during angiogenesis that sprout to form new vessels. Tip cells have filopodia that express high levels of FLK1 and VEGFR-3 that extend out toward VEGF signal that comes from developing embryonic organs and by endoderm.
  3. What is Flt1 involved in and what is its function?
    It is involved in beginning angiogenesis and functions to prune, remodel, and allow for outgrowth of capillaries.
  4. What factors are involved in the final steps (maturing) of angiogenesis?
    PDGFR and TGF-betaR are involved in the final steps of remodeling and connecting arteries and veins.
  5. What role does Notch have in angiogenesis?
    Tip cells express Notch and Notch blocks adjacent cells from responding to VEGFA
  6. What is Vasculogenesis?
    The blood vessels are created de novo from lateral plate mesoderm.
  7. What is the role of Cdx4 in vasculogenesis?
    They become hemangioblasts per Cdx4
  8. What gene decides what the cells ultimate fate during vasculogenesis?
    Notch decides if they become angioblasts or blood cells
  9. How many waves are there in vasculogenesis and what are they?
    Amniotes have 2 waves of vasculogenesis - yolk sac and intraembryonic.
  10. How many main signaling factors are there for vasculogenesis and what are they?
    bFGF or FGF3, VEGF (there are 5 different one), and agiopoietens.
  11. What is the role of bFGF in vasculogenesis?
    VEGF acts through 3 receptors to recruit cells and form sheets and tubes (VEGF or VEGPR null mutant mice lack blood islands and do not undergo vasculogenesis)
  12. Why is the yolk sac important in vasculogenesis?
    It produces RBCs
  13. What is intraembryonic vasculogenesis?
    Forms the dorsal aorta and vessels that connect with capillary networks that form in the mesoderm (only occurs in the embryo). Vasculogenesis is not associated with blood development. Intraembryonic vascular networks arise from individual angioblast progenitor cells and they DO NOT come from larger vessels. **Fgf2 necessary for the generation of hemangioblasts from the splanchnic mesoderm.**
  14. How are arteries and veins different?
    They differ in oxygenated status of blood, muscularity of walls, and presence of valves. It is a closed system and must hook up correctly.
  15. What genes signal to induce arteries, angioblasts, and veins?
    A strong Notch signal, gridlock and ephrin-B2 induce arteries. Small Notch signal induce angioblasts. EphB4 induces veins.
  16. What genes are involved in smooth muscle formation?
    Tie2 and Ang1 are involved in smooth muscle formation.
  17. Describe the morphogenetic events of heart development
  18. What is made from progenitor cells during cardiac morphology?
    Ventricular myocytes, atrial myocytes, endothelial lining of heart and valves, apicardium all derived from the same progenitor cells.
  19. Where do we get heart formation?
    Where BMP, Fgf8, and Wnt coincide.

    • What are the transcription factors that are crucial for heart development?
    • GATA4 and Nkx2-5. GATA4 is turned on first, then Nkx2-5, then they form a positive feedback loop.
  20. What are the roles and function of Tbx5?
    • Tbx5 is important for cardiac development and is initially expressed in the entire ventricular primordial heart field and later becomes restricted to the right atrium, left atrium, and left ventricle. This restriction of Tbx5 expression leads to right ventricle development in a 4 chambered heart. Tbx5 restriction is necessary for 4 chambers.
    • Where do neural crest cells derive from?
    • They come from the dorsal neural tube and then detach and undergo a transition to a mesenchymal form and detach from the neural tube.
  21. What separates the pulmonary artery and aorta and where do the cells come from?
    The septa separates the truncus arteriosus into the pulmonary artery and aorta form from cells of the cardiac neural crest.
  22. What role does cell death have in forming the heart?
    Cell death of aortic arches is necessary for normal aortic development.
  23. What can defects of formation of the pouch of the embryonic gut lead to?
    Esophagotracheal fistulas
  24. What is formed from the pouch of the embryonic gut?
    The trachea and esophagus
  25. Describe how branching morphogenesis shapes the lung from the center branches outwards?
    Branching morphogenesis involves growth from the center outward, like the way a tree grows. This means that the first bronchial branches form first. Subsequent branches produce more distal bronchial branches. The lung bud responds to left-right asymmetry cues including Tgfbeta-related molecules, such as activin receptor 3, Lefty1, Lefty3 and growth differentiation factor 1, and by the bicoid type homeobox gene Pitx2.
  26. How many lung lobes do humans and mice have?
    Humans have 2 left lobes and 3 right lobes. Mice have 1 left lobe and 4 right lobes.
  27. What genes regulate the branching morphogenesis?
    TGFbeta/BMP and FGF signaling pathways
  28. What type of signaling is required to promote distal fate of the lungs?
  29. What form the primitive alveolar sacs?
    The terminal branches of the lungs and coordinated development of vasculature, smooth muscle, and differentiation of type II and type I alveolar cells is required.
  30. What are type II alveolar cells?
    They are cubiodal cells that can regenerate or form type 1 cells and produce surfactant.
  31. What are type I alveolar cells?
    Cells that flatten and enable greater gas exchange.
  32. What is surfactant of the lungs?
    Production of surfactant is a key step in the transition to air breathing and forms a physical barrier between gas and liquid in the alveoli and reduces surface tension. It keeps aveoli from collapsing.
  33. When the digestive system tube closes and constricts posterior to the pharynx what is formed?
    The esophagus, stomach, small intestine, and large intestine.
  34. What is the digestive system formed from?
    The endoderm. The endoderm only forms the lining of the tube. Cells from the splanchnic and lateral plate mesoderm will surround the tube and form the smooth muscle.
  35. What is developed from the digestive tube?
    The esophagus, stomach, liver, pancreas, intestines, and cloaca.
  36. What is necessary forperistalsis?
    Smooth muscle
  37. What are the cellular events and critical signaling pathways involved in the formation of the digestive tract (stomach, small intestines, and colon), associated glands (liver, pancreas, and gall bladder) and biliary ducts.
  38. What signaling is important for the formation of the hepatic endoderm?
    Positive signaling from the cardiogenic mesoderm and inhibition by notochord, ectoderm, and mesenchyme.
  39. What is derived from the ventral outgrowth of the distal foregut, the hepatic diverticulum?
    In the 4th week, the liver, gallbladder, and biliary duct system
  40. Where does the hepatic diverticulum grow and what does it give rise to?
    Between the layers of the ventral mesogastrium to give rise to the primordium of the liver.
  41. What do the proliferating endoderm give rise to?
    Hepatocytes and epithelial lining of the intrahepatic duct.
  42. What does the caudal part of hepatic diverticulum become?
    The gallbladder and cystic duct.
  43. What do the cystic duct of the gallbladder and hepatic duct of the liver comprise?
    The extrahepatic biliary duct (bile duct). The duct is occluded with epithelial cells and must undergo canalization to form functional ducts.
  44. How does the pancreas form?
    The pancreas develops from two buds from the gut tube, the ventral and dorsal pancreatic sections. These sections fuse to form the pancreas.
  45. Which pancreatic bud rotates and what direction does it rotate?
    The ventral pancreatic bud rotates around clockwise to the dorsal pancreatic bud and fuses
  46. How and when does the formation of the small intestines and colon occur?
    At 5 weeks, the midgut is attached to the dorsal mesentery and communicates with the yolk sac via the vitelline (omphaloenteric) duct. It is supplied blood by the superior mesenteric artery. The midgut is divided into the cranial and caudal limbs based on attachment to vitelline duct.Rapid elongation of the cranial limb and its mesentery. Rotation of limbs along the axis of the superior mesenteric artery.Cuadal limb of midgut rotates to cranial position. A retraction of the herniated loops occurs in the 10th week in association with expansion of the abdominal cavity. The cecum is the last part of the gut to re-enter. It descends into the right iliac fossa. The distal end of the cecum forms the appendix, a narrow diverticulum, at this time. The ascending and descending colon and duodenum reattach to the dorsal abdominal wall (retroperitoneal) fixing the position of the organization of the intestines.
  47. What does the cranial limb give rise to?
    The duodenum and jujenum.
  48. What does the caudal limb will give rise to?
    The ileum, cecum, appendix, ascending colon, and 2/3 of the transverse colon.
  49. How and when does the opening the lumen of the intestinal tract occur?
    In the 5th week, the epithelium of the small intestines proliferate. Intestines are occluded by a solid plug by the 6th to 7th week.Through the process of recanalization, a secondary lumina appears. The mesoderm aggregates and pushes into the epithelium to form intestinal villi. Epithelium transforms into a simple columnar epithelium.
  50. How does Partitioning of the cloaca occur?
    The hindgut ends with the cloacal membrane � composed of endoderm and ectoderm of anal pit (proctodeum). Cloaca is divided by urorectal septum. Urorectal septum grows toward the cloacal membrane through infolding of lateral cloacal wall. Septum ultimately leads to the separation of the cloaca into the rectum and cranial anal canal and the urogenital sinus.
  51. What are the common abnormalities of the liver and gallbladder?
    Variations in the liver lobulation is common but not clinically significant. Accessory hepatic ducts and duplication of the gallbladder are also common and usually asymptomatic. Extrahepatic biliary atresia � blockage of the biliary tracy that occurs in 1 in 15,000 live births. This leads to jaundice � yellow coloration due to buildup of bile entering the blood.
  52. Defects of pancreas development?
    Annular pancreas. The ventral pancreatic bud can form as two lobes with common duct. If the two lobes migrate in opposite directions around the duodenum, they can compress the duodenum and cause gastrointestinal obstruction.
  53. Defects in the gut development?
    Congenital omphalocele. Persistent herniation of abdominal contents with a proportionally smaller abdominal cavity. The hernia sac is covered by the epithelium of the umbilical cord.
  54. Defects of cloacal partitioning?
    abnormal development of the urorectal septum, Anorectal Agenesis, Anal stenosis, Membranous atresia of anus, A failure to the anal membrane to perforate at the end of the 8th week.
  55. What is urorectal septum?
    Anorectal defect. Can occur with or without a fistula. Most common type of anorectal defects.
  56. What is Anal stenosis?
    The result of a narrow anus and anal canal. Believed to be caused by dorsal deviation of urorectal septum.
  57. What is membranous atresia of anus?
    The result of a thin layer of tissue obstructing the anal canal.
  58. What are the pronephros?
    Pre-kidneys that appear in the 4th week of development and are NOT functional
  59. What are the mesonephros?
    Pre-kidneys that appear late in the 4th week and functions for about 4 weeks.
  60. What are the metanephros?
    develops between 5th and 15th weeks and becomes the functional kidney. A metanephric blastema develops from intermediate mesoderm on each side of the body axis early in the 5th week. Simultaneously, each mesonephric duct sprounts a uretic bud that grows into each metanephric blastema. By the 6th week, the ureteric bud bifurcates and the two growing tips (ampullae) induces cranial and caudal lobes in the metanephros. Additional lobules form during the next 10 weeks in response to further bifurcation of the ureteric buds.
  61. What happens with the kidneys at 6-9 months?
    They rotate and relocate.
  62. What is polycystic kidney disease?
    Autosomal dominant polycystic kidney disease incidence of 1/400-1/1000. 85% of the patients having a mutation of the PKD1 gene. Mutations have also been found on related PKD2 and PKD3 genes. Cysta normally appear adults around 10 years of age. Polycystic kidney disease is associated with an abnormal rate of tubule divisions, with hypoplasia of portions of tubules left behind as the ureteral bud advances.
  63. What is renal agenesis?
    Unilateral renal agenesis occurs at an incidence rate of 1/1000. The remaining kidney undergoes compensatory hypertrophy, which leads to an asymptomatic condition. Bilateral renal agenesis occurs at an incidence rate of 1/3000.
  64. What is a horseshoe kidney?
    At an incidence rate of 1/600, the kidneys fuse at the midline to form a horseshoe kidney. The fusion is believed to occur during the 5th week of development when the two developing kidneys lie very close to each other. Approx. 7% of persons with turner�s syndrome (XO) have horseshoe kidneys.
  65. Describe the morphological process of development of the testes?
    Need AMH and testosterone, which causes degeneration of the Mullerian duct. Testosterone induces Wolffian duct to differentiate into epididymis, vas deferens, and seminal vesicles and induces urogenital swellings to develop into the scrotum and penis.
  66. What does the Wolffian duct differentiates into?
    The vas deferens, epididymis, and seminal vesicle.
  67. Describe the morphological process of development of the ovaries?
    The Mullerian ducts develop while Wolffian ducts degenerate. Mullerian duct differentiates into the oviduct, uterus, cervix, and upper portion of vagina. Paramesonephric ducts form and will become the fallopian tubes. Estrogen from mother and genital tract induced female phenotype in XO
  68. What are the embryonic origins and adult function of Sertoli cells, Leydig cells, and granulosa cells?
    The genital ridge.
  69. All sexually reproducing animals arise from what?
    The fusion of germ cells.
  70. How do progenitors of germ cells arise?
    1) germ cells determined by autonomous cytoplasmic determinants (germ plasm) 2) Germ cells specified by inductive interactions between cells.
  71. Are PGCs morphologically distinct during early development?
  72. What induced germ cells and where do they form?
    bone morphogenic proteins. The germ cells form at the junction of the extraembryonic ectoderm, epiblast, primitive streak, and allantois.
  73. What do PGCs express to BMP?
    fragilis and stella
  74. Migration of PGC?
    At e7 the cells leave the posterior primitive streak, and enter the endoderm. They enter the hindgut and migrate dorsally until e9. Then they exit the hindgut and stall, then at e10, they enter the genital ridges. E11.5 they enter the gonad. The population proliferates to 2500-5000 PGC during migration. In the gonad mitosis, the population continues to increase the number of PGCs.
  75. What does the genital ridge turn on?
    SF-1, WT1, LHX9, WNT4, SOX9, FGF9, and GATA4 in both male and female creating a bipotential gonad.
  76. SRY?
    Important to make males. SRY is the sex determining region of the y chromosome and has 223 amino acids. It contains a high mobility group box (HMG box) � therefore it is likely a transcription factor. SRY is a mammalian gene only. Sry is detected in XY and rare XX males, but absent from XX and XY females. There is evidence that SRY is testis determining factor.
  77. Where is SRY expressed?
    In testis and in the somatic cells of indifferent gonad immediately before and during testis differentiation.
  78. Sox9 ?
    turns on SF-1 and FGF9 leading to male fate. SRY turns on Sox9. Autosomal HMG box protein, ma be a transcription factor. At time of sex determination Sox9 migrates into the nucleus and binds to AMH/AMF promoter. May also be a splicing factor � can replace missing splicing factors in experimental splicing assays. XX humans that have an extra copy of Sox9 develop as males even without SRY
  79. RSPO1?
    Soluble protein, binds to receptor and activates Disheveled. Disheveled, part of the Wnt pathway increases active beta-catenin. Beta catenin acts in a positive feedback loop with Wnt4 and Rspo1. XX individuals with RSPO1 mutations are phenotypically male. RSPO1 is absolutely critical for development of ovary (and external genitalia)
  80. Wnt4?
    Turns on Rspo1 and they turn on beta-catenin, which turns off Sox9 and leads to female fate. Expressed in the genital ridge at bipotential stage, and is maintained ony in XX gonads. Beta-catenin is activated and it initiates the ovary differentiation pathway. In Wnt4 -/- mice, the ovary does not form properly and cells express testis specific genes including AMH/AMF and testosterone.
  81. Dax1?
    Only stays on in females. In males 2 copies of Dax1 leads to gonadal dysgenesis - phenotypical female, male with internal, un-dropped testes, and are infertile. Dax1 is a member of nuclear hormone receptor family. Expressed in the male and female genital ridges initially. SRY and Dax1 expressed in same cells but eventually Dax1 is expressed solely in the XX gonadal ridge. Antagonizes function of SRY and Sox9 and down-regulated SF1 expression. This is why 2 copies of Dax1 will overcome SRY and Sox9. There is just too much Dax1 protein for Sry and Sox9 to do their jobs
  82. FGF9 in males?
    Necessary for Leydig cells to proliferate. Promotes Sertoli cell differentiation and mesonephric cell migration necessary for testis cords to form.
  83. Fruitless?
    Turned on in the absence of Sx1 and leads to male fate.
  84. What function does estrogen have during secondary sex determination?
    Allows mullerian ducts to develop while the Wolffian ducts degenerate in females.
  85. What functions do AMH and testosterone have during secondary sex determination?
    In males AMH and testosterone is absolutely crucial. AMH causes degeneration of Mullerian duct. Testosterone induces Wolffian duct to differentiate into epididymis, vas deferens, and seminal vesicles and induces urogenital swelling to develop into the scrotum and penis.
  86. 5 alpha-dihydrotestosterone (DHT) is necessary for and what does lack of 5 alpha reductace cause?
    Promoting development of male urethra, prostate, penis, and scrotum. Humans with a defect in 5 alpha reductase, lack the ability to convert testosterone into DHT. XY children that lack this enzyme are XY, they have functioning undescended testes, enlarged clitoris, and blind vaginal pouch and appear to be female. At puberty increased testosterone levels induce differentiation of external genitalia � penis enlarges and scrotum descends.
  87. Androgen insensitivity syndrome?
    XY individuals that have SRY gene and have testes and make testosterone and AMH but lack testosterone receptor. Respond to estrogen made by adrenal glands and have female appearance but lack uterus and oviducts and have testes in the abdomen.
  88. Explain the aromatase hypothesis?
    CYP19 gene is the aromatase gene. Exposure to atrazine turns off CYP19 which leads to increase of aromatase. Aromatase converts testosterone to estrogen, feminizing the animals.
  89. Describe how location can determine sex?
    Crepidula fornicate (slipper snails) pile up on each other, born male, and if attached to a female will become male. If they are removed from female attachment, they become female. Also if there is a large population of males, some will become female.
  90. Where do neural crest cells derive from?
    The dorsal neural tube and detach. Epithelial neural tube cells undergo a transition to a mesenchymal form and detach from the neural tube.
  91. Important characteristics of the neural crest?
    1) Neural crest migrates from the dorsal neural tube 2) Migration can be segmented specific in the cranial region 3) Migration is through rostral somites from ephrin signals 4) Neural crest is prepatterned 5) Neural crest is pluripotent and can differentiate into the types of tissues that ectoderm and mesoderm typically generate 6) Neural crest disorders are called neurocristopathies
  92. Where do the trunk neural crest migrate through?
    Specifically through the rostral/anterior somites. Neural crest migration avoids ephrin proteins of the caudal/posterior sclerome.
  93. Neural crest can differentiate into?
    Multiple cell types depending on genetic regulation
  94. What parts of the craniofacial development involves segmentation?
    The pharyngeal region and hindbrain are highly segmented whereas segmentation is less evident in the forebrain and midbrain.
  95. What forms the skeletal and muscle element?
    Considerable cranial migration of neural crest cells, paraxial mesoderm, and prechordal mesoderm.
  96. Development of the pharyngeal (brachial) arches
    Appear by the end of the 1st month. 4 lateral pairs of endodermally � lined outpocketings called pharyngeal pouches and an unpaired ventral midline diverticulum, the thyroid primordium. 4 pairs ectodermally covered inpocketing called pharyngeal grooves. Alternating with the pharyngeal grooves and pouches are paired masses of mesenchyme called pharyngeal arches. Central to each pharyngeal arch is prominent artery called an aortic arch, cartilage and nerve and skeletal muscle
  97. What muscles and bones come from pharyngeal arch 1?
    Bone - Malleus, Incus, Meckel�s cartilage. Muscle � temporalis, masseter, mylohyoid
  98. What muscles and bones come from pharyngeal arch 2?
    Bone - Stapes, styloid process, hyoid bone. Muscle � frontalis, buccinators, oris, oculi, occipitalis, platysma
  99. What muscles and bones come from pharyngeal arch 3?
    Bone - hyoid bone. Muscle � stylopharyngeus
  100. What muscles and bones come from pharyngeal arch 4 and 5?
    Bone- thyroid and cricoid cartilage. Muscle � pharyngeal muscles
  101. Cleft lip and cleft palate ?
    Cleft lip results of a lack of fusion of maxillary and nasomedial processes. Bilateral cleft occurs when the entire premaxillary segment is searate from both maxillae. Premaxillar segment commonly protrudes past the normal facial contours. Caused by hypoplasia of the maxillary process
  102. How does the neural crest helps develop the peripheral nervous system?
    It develops the melanocytes, dorsal root ganglia, dermomyotome, chain ganglia, dorsal aorta, preaortic ganglia, enteric nervous system. The chain ganglia are laid down by neural crest cells that migrate from the closing neural tube.
  103. Ametabolous?
    Adult is just a larger version.
  104. Hemimetabolous?
    adult has some changes
  105. Holometabolous?
    complete metamorphosis from larva to adult form
  106. What are imaginal discs?
    Undifferentiated tissues within larval insects that are patterned to form adult tissues in holometabolous insects.
  107. Define regeneration?
    Growth of amputated body parts or nonfunctioning organs. The new tissue is considered to be identical to the previous tissue. Usually envisioned as the replacement of complex, multi-tissue structures. Requires de novo patterning of the tissue. Example � limbs/digits, tails/fins, liver
  108. Repair?defined as a closely related process that is defines as replacement of singular tissue type. The repair is not always with the same cell type. Example � skeletal muscle
  109. Morphallactic regeneration?
    Regeneration that occurs through the repatterning of existing tissues with little new growth. Hydra are an example.
  110. Compensatory mechanism?
    When differentiated cells divide while maintaining their differentiated functions. Zebrafish heart regenerates from cardiomyocytes. The cardiomyocytes are able to proliferate to form new heart muscle, unlike mammalian cardiomyocytes
  111. Epimorphosis?
    dedifferentiation of adult structures to form an undifferentiated mass of cells that then can be respecified. Best studies example is Salamander limb regeneration. All of the cells are present in the new limb � skeletal muscle bone, cartilage, tendons, nerves, vascular, epidermis.
  112. Dedifferentiation?
    many differentiated cells have lost the ability to undergo cell division. The ability to regenerate by epimorphosis is dependent on thee cells retaining the ability to re-enter the cell cycle.
  113. Explain key steps in the regeneration of an amphibian limb?
    1) Epidermal cells adjacent to the stump migrate to cover the wound surface. Proloferation of hese cells will lead to the apical ectodermal cap (AEC). This is distinct from normal wound healing � no scar and dermis does not follow the epidermis. 2) The nerves degenerate at the site of the amputation. 3) Bone, cartilage, myocytes, and neurons dedifferentiate and become detached from one another. These cells migrate under the AEC t form the regeneration blastema. Differentiation gene transcription decreases. Mesenchyme proliferating gene transcription increases. 4) blastema cells redifferentiate to form the new structures of the limb.
  114. The blastema?
    has an apical ectodermal cap, like the AER, and cells that derive from dedifferentiation.
  115. Does limb regeneration shares similarities to limb bud development?
    Yes, the limb bud has AER and progress zone in the mesenchyme. Regenerating limb has AEC and regeneration blastema in the mesenchyme. Limb regeneration is dependent on the interaction between mesenchyme and ectoderm. The progress zone can be replaces with regeneration blastema in the limb bud. The same patterning signals control both processes.
  116. Stem cell mediated?
    tissue specific adult stem cells serve as source of cells for regrowth. Several cell types have been identified in mammals that possess stem cell-like properties but are specified to one or a few cell fates. Satellite cells - skeletal muscle. Neural stem cells - neurons. Hematopoetic cells - blood cells, dendrytic cells, osteoclasts. Cardiac stem cells - cardimyocytes. Bulge cells - follicular cells and melanocytes
  117. Teratogens?
    • act with specificity, they produce specificabnormalities at specific times during gestation. Specificity also applies to species, for example, aspirin and corticosteroids have been found to be teratogenic in mice and rats but appear to be safe in humans. They may have a dose-effect relationship. They must reach the developing embryo at a sufficient concentration to cause their effects.
    • Potential mechanisms of teratogenic effects of ethanol ?
    • Altered neural crest migration - ethanol treated neural crest cells prematurely initiate their differentiation into facial cartilage. Apoptosis of neurons - through the generation of ROS. Block the adhesive function of the L1 protein, similar to mutations in L1
  118. Thalidomide?
    was marketed as a sedative and given to pregnant women as an anti-nausea med. Children were born with flipper like limbs. Severity depended on the time and duration of exposure to the drug.
  119. Veratrum californicum?
    skunk cabbage. Sheep eat it� if they eat it when they are pregnant it causes severe neurological defects including cyclopia. Jervine and cyclopamine are made by the plant - jervine inhibits cholesterol synthesis and cyclopamine blocks SHH function. Sheep die at birth, lack pituitary and have severe brain defects.
  120. Fetal alcohol syndrome (FAS)
    third most prevalent form of mental retardation. Symptoms � mental retardation, small head, indistinct philtrum, narrow upper lip, brain abnormalities. Affects 1 out of every 500-750 births in the US.
  121. Syndromic defects associated with RA?
    characteristic set of defects absent or small jaws, cleft palate, aortic arch abnormalities, thymic deficiencies, abnormalities of CNS. Mechanism � alteration of Hox gene expression that results in altered anterior-posterior patterning. Cranial neural crest stop both migration and proliferation.
  122. Valproic acid and carbamazepine?
    both are anti-seizure medications. Exposure in-utero carries 1% risk of neural tube defects (x10 normal risk).
  123. Fetal valproate syndrome?
    an associates pattern of malformations, clinical features include cranial facial abnormalities, small mouth, cardiovascular defects, long fingers/toes, hyperconvex fingernails, and cleft lip
  124. Edocrine disruptors?
    exogenous chemicals that interfere with the function of hormones, special class of teratogens. Mechanisms: 1) mimic - acts like a natural hormone 2) blockers - block the binding of a hormone to its receptor or blocks the synthesis of the hormone 3) triggers - bind to hormone receptors and elicits an abnormal response
  125. Diethylstilbestrol (DES)?
    synthetic estrogen. Prescribed in the 1930-70�s for women who had experienced miscarriages or premature deliveries. In 71 the FDA stopped it from being prescribed to pregnant women because it was linked to vaginal cancer in female offspring.
  126. Defects of DES daughters?
    cervical hood, abnormally shaped cervix, adenosis, fallopian tube abnormalities, abnormally shaped uterus, higher rate of infertility, and increase risk for developing clear adenocarcinoma of the cervix and vagina.
  127. DES in men?
    causes defects in reproductive tract, abnormal genitalia, in mice exposure results in infertility, no clear in humans.
  128. What genes do estrogen and progesterone regulate?
    the 5� Hoxa cluster � Hoxa-9, a10, a11, and a13. Hox genes are homeotic genes that control development of structures along anteroposterior axis. They are organized into clusters on certain chromosomes.
  129. What develops from HoxA-13?
  130. What develops form HoxA-11?
  131. What develops from HoxA-10?
  132. What develops from HoxA-9?
    oviducts (fallopian tubes)
  133. What does DES misregulates?
  134. Mechanisms of DES action?
    Binds to estrogen receptor. The estrogen receptor in turn represses Wnt7a expression. A lack of Wnt7a misregulates Hox gene expression.
  135. Bisphenol A (BPA)?
    A xenoestrogen found in polycarbonate plastics, water, baby bottles, medical devices.
  136. Reproductive problems associated with BPA?
    Mice exposed in utero to BPA levels consistant with human dietary levels had meiosis defects that resulted in aneuploides. Dysmorphology of sex organs, low sperm counts and behavioral changes associates with fetal exposure in animals.
  137. Mechanisms of BPA action?
    • Competes with estradiol foe estrogen receptors in MCF7 breat cancer cells
    • Viclozolin is?
    • a dicarboximide non-systemic pestiside used to control fungi in vines, strawberries, veggie and fruits. It is an anti-adrenergic endocrine disruptor
  138. Viclozolin mechanism of action?
    1) Targets androgen receptor (AR) to nucleus. 2) In the presence of DHT-blocks androgen induces gene expression by blocking AR from binding to androgen response elements in the DNA 3) In the absence of DHT-induces AR to bind DNA and activate androgen responsive genes 4)This agonist/antagonist dual function poses serious risks for normal sexual differentiation and fertility in men exposed to vinclozolin.
  139. Transgenerational effects over time?
    Beyond the exposed generation. Vinclozolin exposed rate in f5 generation have stable epigenetic changes that are noted and disease rates are being observed that are similar to those exposed in utero. Children born to thalidomide exposed parents have 5x the rate of limb abnormalities.
  140. Phenylketonuria (PKU)?
    Autosomal recessive disorder that occurs in all ethnic groups, but most common in northern European ancestory. Due to a deficiency in the enzyme phenylalanine hydroxylase (PAH). Phenylananine accumulates and is converted into phenylpyruvate. This buildup causes mental retardation, the severity of which is a spectrum. If untreated most cases are associated with an IQ under 30. Treatment � main treatment is a strict diet with very limited intake of phenylalanine (low protein). Avoid foods made with aspartame it releases phenylalanine when digested. Phenylalanine-free formula. Defects in 3 other enzymes can cause PKU. These enxymes are cofactors
  141. Classic Maple Syrup Urine Disease (MSUD)?
    An autosomal recessive trait. The baby appears normal at birth, but develops poor feeding and vomiting during 1st week of life. Lethargy and coma may follow soon. Hypoglycemia is common, and baby will die within a few weeks if undiagnosed.
  142. Defects of degredation of valine, leucine, and isoleucine?
    These are branched chain hydrophobic amino acids. Deficiency of any degradative enzymes except transaminases results in acidosis. Decarboxylation of leucine, isoleacine and valine done by complex enzyme system �branched chain alpha ketoacid dehydrogenase that uses thiamine pyrophosphate (vit B1) as a coenzyme. Deficiency of alpha-ketoacid dehydrogenase causes MSUD named for sweet odor of urine.
  143. Diagnosis of MSUD?
    Often first suspected due to peculiar odor of urine. Confirmed by amino acid analysis showing marked elevations of leucine, isoleucine and valine and alloisoleucine in the plasma or high levels of leucine, isoleucine and valine and their respective ketoacids in urine.
  144. Progeria?
    Causes children to age rapidly and die as early as 12, usually from heart failure or strokes. Babies appear normal in infancy but have profound growth failure during the 1st year. 90% of children with progeria have a mutation on the gene that encodes the protein lamina a. Splicing occurs abnormally, we get truncated lamin A protein. Dominant inheritance, but not genetic, so each child may be a sporadic mutation. The truncated protein lamin A causes nuclear morphological abnormalities, disorganization of heterochromatin, and defective repair of DNA damage and increased genomic instability. Characteristics � short stature, low weight, loss of subcutaneous fat, head large for face, prominent scalp veins, alopecia, delayed and abnormal dentition, stiff joints, no sexual maturation. These children DO NOT experience dementias.
  145. Treatment of progeria?
    Short term - dialysis clears the body fluids. Long term -diet low in branched chain amino acids with carefully added synthetic valine, leucine, and isoleucine. Prognosis - severe ketoacidosis, cerebral edema, and death may occur with stressful situation, infection, surgery. Mental and neurological deficits are common.
  146. Angelman syndrome ?
    complex genetic disorder that primarily affects the nervous system caused by deletion of the maternal chromosome 15 or by paternal uniparental disomy. occurs when there is a problem with the maternal genes and the offspring only gets the paternal genes. Chracteristics � developmental delay, intellectual disability, sever speech impairment, and problems with movement and balance. Most affected children also have recurrent seizures and microcephaly. Usually have a happy, excitable demeanor, hyperactivity and short attention span, and difficulty sleeping and need less sleep than usual.
  147. Prader-Willi syndrome?
    Occurs when there is a problem with the paternal genes and the offspring only get the maternal genes. So, caused by deletion in the paternal chromosome 15 or by maternal uniparental disomy. Characterized by hypotonia, feeding difficulties, poor growth, and delayed development. Affected individuals develop an insatiable appetite and chronic over-eating. They typically have mental retardation or learning disabilities and behavioral problems. Genitals in males and females are underdeveloped and usually infertile.
Card Set
Devel. bio exam 3 sg cards.txt
BIO351 Exam 3