LEC 30

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LEC 30
2015-11-23 11:45:44
lec30 lec 30 neuro

Lecture 30 Neuro
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  1. The developing neural tube is patterned along which axis?
    Anterior-Posterior axis (AP)
  2. What are the 4 regions of the “pipe” structure?
    • Forebrain
    • Midbrain
    • Hindbrain
    • Spinal cord
  3. What are the 5 morphological structures of the brain? Where are they located?
    • Telencephalon: forebrain
    • Diencephalon: forebrain
    • Mesencephalon: midbrain
    • Metencephalon: hindbrain
    • Myelencephalon: hindbrain
  4. What regions are formed from the telencephalon?
    • Olfactory bulb
    • Cerebral cortex
    • Hippocampus
    • Basal ganglia
  5. What regions are formed from the diencephalon?
    • Retina
    • Thalamus
    • Hypothalamus
  6. What regions are formed from the mesencephalon?
  7. What regions are formed from the metencephalon?
    • Cerebellum
    • Pons
  8. What regions are formed from the myelencephalon?
  9. When is the layout of the brain specified?
    Early in development
  10. There is a clear separation between which two regions?
    Brain and spinal cord
  11. What portions are included in the three-vesicle stage?
    • Proencephalon
    • Mesencephalon
    • Rhombencephalon
    • Caudal neural tube
  12. What portions are included in the five-vesicle stage?
    • Telencephalon; Lateral ventricle
    • Diencephalon; Third ventricle
    • Mesencephalon; Cerebral aqueduct
    • Metencephalon; Fourth ventricle
    • Myelencephalon; Fourth ventricle?
    • Spinal cord; Central canal
    • Neural retina and lens
  13. What is wnt?
    Secreted molecule in the neural plate
  14. What is wnt’s role?
    Signaling is important for patterning the neural plate along the anterior-posterior axis
  15. At what stage does wnt signaling happen?
    Very early stage
  16. There is a clear distinction between which two regions of the brain?
    • Midbrain and hindbrain
    • MHB
  17. Which region is there high wnt secretion? Low secretion?
    • High: hindbrain (posterior)
    • Low: forebrain and midbrain (anterior)
  18. What are the segments of the hindbrain called?
  19. What are rhombomeres?
    • Segments of the hindbrain
    • Literally, bumps. Series of bumps.
  20. When are specializations in the hindbrain shown?
    Later in development
  21. What do rhombomeres do?
    • Give rise to various structures
    • Express different genes during development
  22. What’s contained in the rhombomeres?
    The soma (cell body) of the motor neurons of different cranial nerves
  23. What are homeotic genes?
    Genes which regulate the development of anatomical structures in various organisms
  24. In what species were “homeotic” genes originally identified?
    Drosophila (fruit fly)
  25. What are responsible for establishing body plan along AP axis?
    Transcription (tx) factors in homeobox genes
  26. What are transcription factors in homeobox genes responsible for?
    Establishing body plan along AP axis
  27. Where are homebox genes clustered?
    In the genome/chromosome
  28. What does the order of the cluster of transcription factors correlate with?
    Order of importance of expression along AP axis
  29. Which genes in vertebrates and humans are related to fly homeobox genes?
    Hox genes
  30. How are hox genes expressed?
    In overlapping domains along the AP axis of the developing brain and spinal cord
  31. Where are the hox genes clustered?
    In the genome
  32. Hox genes are implicated in determining the identity of what?
  33. Rhombomere fate and identity is determined by what?
    Hox genes
  34. The boundaries of hox gene expression coincide with what?
    Rhombomere boundaries
  35. Paralog genes
    • Genes related by duplication within a genome
    • Evolve new functions, even if they are related to the original one
    • Expression is correlated with order and structure
  36. Anterior of hox genes coincide with what?
    Anterior of rhombomere
  37. Which motor neurons occupy the rhombomeres?
    • Trigeminal Nerve (r2 and r3)
    • Facial Nerve (r4)
    • Abducens Nerve (r5)
    • Glossopharyngeal Nerve (r7)
    • Vagus Nerve (r8)
  38. What happens when you genetically delete Hoxa1(-/-)?
    • Decrease in the number of rhombomeres (about 5 vs. 7 rhombomeres)
    • Expansion of r3; loss/reduction of r4 and r5
    • Loss of abducens; reduction of facial nerves
  39. What regulates Hox expression?
    Retinoic acid
  40. What happens with retinoic acid as you go from r1 to r7?
    Production and secretion of retinoic acid increases
  41. Where is retinoic acid produced at the highest level?
    Posterior of hox genes and hindbrain (r7)
  42. What does the sensitivity to retinoic acid mean?
    • Most sensitive can be activated with lowest RA concentration
    • Least sensitive with higher concentration
  43. Which part of the gene and hind brain is most sensitive to retinoic acid? Least?
    • Most- anterior
    • Least- posterior
  44. Hindbrain segmentation involves what?
    Hierarchical relationship of genes
  45. What happens when you block retinoic acid?
    • Size of r1-4 increases
    • r4 increases most
    • r5-8 disappears
  46. Why does r5-8 disappear when retinoic acid is blocked?
    • They’re the least sensitive so they need a lot of retinoic acid
    • But since there’s no RA, they try to expand but disappear
  47. Spinal cord is specialized along which axis?
    Dorsal-Ventral axis (DV)
  48. What happens in the ganglion of the dorsal root of the spinal cord?
    Sensory cells send axons in
  49. What happens in the ventral root of the spinal cord?
    Motor neuron cell bodies send axons out
  50. What is between the sensory neurons and the motor neurons?
  51. What is important for induction?
  52. When does specialization start?
    At the tube
  53. Where are most motor neurons located?
    Closer to the floor plate (ventral)
  54. What are the two specializations?
    Floor and roof plate
  55. Define ectopic
    In an abnormal place or position
  56. What happens when you remove or transplant ectopic notochord?
    Notochord induces ventral cell fates
  57. What happens when notochord is removed?
    No floor plate or motor neurons
  58. What happens when notochord is transplanted on the side somewhere?
    See 2 floor plates and 2 places for motor neurons
  59. What does the transplant/removal of the notochord show?
    Notochord is necessary and sufficient for induction of motor neuron cell fate
  60. What happens when you culture intermediate plate explants on floor plate (or notochord) explants?
    Cells adopt ventral cell fates (motor neurons)
  61. What happens when intermediate plate explants are cultured with conditioned medium from floor plate?
    A diffusible factor is the inducer
  62. What does a diffusible factor from floor plate or notochord do?
    Induces motor neurons
  63. What is the signal released by the notochord?
    Sonic Hedgehog (SHH)
  64. What is Sonic Hedgehog?
    • SHH = morphogen
    • Secreted protein expressed early in the floor plate and notochord
    • Signal that induces ventral (MN) fate
  65. What does SHH signaling require?
    The smoothened receptor
  66. What effect does the patch protein normally have on the smoothened?
    Patched inhibits smoothened
  67. What effect does Hedgehog have on the patch protein?
    HH binds to patch to inhibit inhibition
  68. Where in the tube (spinal cord?) is there a high level of BMP?
    In the roof plate
  69. Why is there a high level of BMP dorsally?
    BMP signaling in the ectoderm so when it creates the neural tube, the top of the tube where it’s pinched together is gonna have the BMP signaling
  70. What kind of gradient does BMP have?
    High dorsal, low ventral gradient
  71. What happens when you add an ectopic notochord dorsally?
    • Ventralization of the spinal cord (additional floor plate and motor neurons dorsally)
    • Extinguished BMP expression
  72. What was the point of the dorsal induction experiment of dorsally adding an ectopic notochord?
    Suggests that BMP is needed for dorsalization, but doesn’t prove it
  73. What was the complementary experiment for dorsal induction?
    Removal of the notochord
  74. What was the result of removing the notochord?
    • Lack of ventral phenotype (no floor plate or motor neurons)
    • BMP expressed everywhere
  75. What was the point of the dorsal induction experiment of removing the notochord?
    Suggests that BMP inhibits ventralization, but doesn’t prove it
  76. What are explant co-culturing experiments?
    Culturing intermediate plate (IP) explants on floor plate (FP) explants
  77. What do explant co-culturing experiments show?
    • IP cells adopt ventral cell fates (MN) in absence of BMP
    • If there is BMP in the medium, then BMP inhibits ventralization
    • This shows the role of BMP signaling in repressing ventral fates
  78. What ultimately determines cell fates in the spinal cord?
    Opposing BMP and SHH signaling along DV axis
  79. What are the effects of BMP on the cell fates?
    • Inhibits ventral
    • Induces dorsal
  80. What are the effects of SHH on the cell fates?
    • Induces ventral
    • Inhibits dorsal
  81. What is the effect of the two gradients working in opposition?
    Creates polarity
  82. What do the different cellular responses, according to position of the cell in the concentration gradient of a morphogen (shh or bmp), result in?
    Discrete differences in cell fate along the gradient due to the graded concentration of morphogen
  83. What do the SHH levels determine?
    Ventral fates
  84. What does the particular fate of the different cells in the ventral neural tube depend on?
    • The amount of SHH that they are exposed to
    • Their location on the DV axis
  85. What is the fate of the cells in the ventral neural tube that are exposed to LOW concentration of SHH?
    Ventral interneurons
  86. What is the fate of the cells in the ventral neural tube that are exposed to MEDIUM concentration of SHH?
    Motor neurons
  87. What is the fate of the cells in the ventral neural tube that are exposed to HIGH concentration of SHH?
    Floor plate cells
  88. What does the expression of homeodomain transcription factors allow for?
    A readout of SHH gradient in ventral spinal cord
  89. What does the repression of class I homeodomain protein expression by SHH signaling do?
    Sets discrete boundaries
  90. What are the class I homeodomain transcription factors?
    • Pax7
    • Dbx1
    • Dbx2
    • Irx3
    • Pax6
  91. What are the class II homeodomain transcription factors?
    • Nkx6.1
    • Nkx2.2
  92. Which transcription factors mutually repress each other?
    • Pax6 and Nkx2.2
    • Dbx2 and Nkx6.1
  93. The combination of what determines cell fate?
    Combo of homeodomain proteins/transcription factors expressed
  94. What determines which transcription factor is expressed?
    The level of SHH that the cell sees
  95. What codes for ventral spinal cord cell fates?
    Lim homeodomain?