Lecture 16: Nervous Development I Flashcards

1
Q

Describe the stages of the neural tube wall from that of a simple cuboidal epithelium to a stratified epithelium

A
  • Early neural epithelium: simple cuboidal
  • Neural plate: simple columnar epithelium
  • Early neural tube wall: pseudostratified epithelium, single layer of columnar cells with nuclei at varying heights, limiting membranes=basal lamina (external limiting membrane)
  • Late neural tube wall: stratified epithelium
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2
Q

Describe and explain the importance of the orientation of the metaphase plate during proliferation of cells within the neural tube

A

If metaphase plate is perpendicular to inner margin of neural tube (next to lumen), two resulting daughter cells will remain proliferative

If metaphase plate is parallel to inner margin…

  • Daughter cell closest to lumen will: remain proliferative
  • Daughter cell further from lumen will: Express Notch receptor, Become postmitotic, Move to the external limiting membrane, Become a neuroblast (pre-neuron)
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3
Q

Describe the hierarchy of basic cell lineages in the development of the nervous system and note when mitosis ceases in each lineage and differentiation begins

A
  • Neuroepithelium refers to the initial epithelial layer of the neural tube
  • Bipotential progenitor cell refers to the fact that his cell has been restricted to one of the two pathways: neuronal lineage progenitor or glial lineage progenitor
  • Neuronal lineage cells are committed to developing into neurons; they are postmitotic
  • Glial lineage cells have a number of paths leading to types of glial cells
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4
Q

Describe the experiments where one grafts a secondary notochord, removes the notochord, and slits the neural plate on one side of the floor plate

A
  1. Grafting an extra notochord near the neural tube induces a secondary floor plate.
  2. In the absence of a notochord, a very incomplete floor plate forms, and nerve fibers exit from multiple sites around the spinal cord.
  3. Slitting the neural plate on one side of the floor plate removes the wall of the neural tube from the influence of the notochord, allowing the disorganized exit of nerve fibers from that part of the spinal cord.
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5
Q

Describe the signaling pathways and factors that establish the dorsal-ventral axis of the developing neural tube. What roles do the notochord and non-nervous ectoderm play?

A

Ventral Signaling

  • The notochord induces formation of the floor plate of the neural tube via sonic hedgehog (Shh)
  • Sonic hedgehog produced by the floor plate induces the formation of motor neurons

Dorsal Signaling

  • Ectoderm flanking the neural plate uses BMPs to induce snail-2 in the future neural crest and later to maintain Pax-3 and Pax-7 to create a dorsalizing effect
  • The expression of Pax-3 and Pax-7 is suppressed by Shh from the floor plate to suppress the dorsalizing effect in the basal plate
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6
Q

Describe the relationship between rhombomeres, cranial nerves, and pharyngeal arches.

A

The cranial nerves, which have a highly ordered pattern by which they supply structures derived from the pharyngeal arches and other structures in the head, have an equally highly ordered origin with respect to the rhombomeres (which are just a highly ordered expression of different transcription factors that show a morphological reflection)

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7
Q

What pharyngeal arches are associated with which cranial nerves?

A

Cranial Nerve V: first pharyngeal arch

Cranial Nerve VII: second pharyngeal arch

Cranial Nerve IX: third pharyngeal arch

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8
Q

How is the segmented nature of spinal nerves related to the somitic mesoderm pattern?

A
  • Segmented nature of spinal nerves is due to pattern of somatic mesoderm along neural tube
  • Motor neurons can penetrate anterior mesoderm of somites but not posterior mesoderm of somites
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9
Q

What is the role of the isthmic organizer, and what signaling/transcription factors are involved?

A

It is a signaling center!

It’s signaling molecule is FGF-8/Wnt to induce expression of En-1, En-2, Pax-2, Pax-5

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10
Q

How does shh determine the midbrain dorsoventral axis?

A

Shh restricts ventral expression of molecules, such as Pax-7, which are characteristic of the alar plate.

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11
Q

What role do prosomeres P1-P3 play in the forebrain patterning?

A
  • P1-P3 define the diencephalon
  • P2-P3 define dorsal and ventral thalamus
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12
Q

What is the relationship between Shh and holoprosencephaly?

A

Similar to the spinal cord, the ventral forebrain is induced and organized by shh, secreted by midline axial structures. In the absence of shh signaling in this area, the tissues of the ventral forebrain are greatly reduced, leading to midline fusion of the optic vesicles and a general reduction of the growth of the midface region. This situation results in a type of anomaly called holoprosencephaly (no proencephalon), which in extreme cases is accompanied by cyclopia (orbits of eyes are not formed into two cavities)

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13
Q

Describe steps in the outgrowth of a motor neuron and compare with a sensory neuron

A

Motor axon outgrowth:

  • Axon grow out from the motor neuroblasts located in the basal plate of the spinal cord
  • Boundary caps created by neural crest cells maintain separation between central nervous system components and peripheral nervous system components

Formation of a sensory neuron:

  • Cell bodies of sensory neurons are derived from neural crest cells
  • Cell bodies of sensory neurons form sensory spinal ganglia
  • Axons grow from these cell bodies toward the spinal cord and the periphery
  • Boundary caps maintain separation here as well
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14
Q

What are growth cones?

A
  • Characterized by expanded region of cytoplasm with filopodia
  • Growth cones advance via extension/resorption cycles that involve actin microfilaments
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15
Q

How do environmental factors effect growth?

A

They can cause chemoattraction, contact attraction, chemorepulsion, contact repulsion

  • some environments give growth cones signals to continue extending forward, whereas other environments give “stop” signals or “turn” signals. The sensitivity of growth cones to their environment is so great that they may be able to discriminate a concentration difference of as little as one molecule across the surface.
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16
Q

What role do netrins and semaphorins play in outgrowth of neurons?

A

Netrins: family of chemoattractants, attractant substances

Semaphorins: family of chemorepulsives, repulse diffusible substances

17
Q

What are boundary caps and what role do they play in axon growth?

A

They act as selective filters, allowing the free passage of outgrowing and ingrowing axons between the neural tube and the periphery, but serve as a barrier to keep cells in their appropriate compartment.

In the absence of boundary caps, many cell bodies of motoneurons translocate away from the lateral motor column (their normal location) into the space outside the neural tube.

18
Q

List cues involved in axon guidance

A
  • Caudal half of somite
  • Fibronectin and laminin
  • Integrins and cadherins
19
Q

What are pioneering axons?

A

The proceeding axon to which others follow, growing towards its target.

20
Q

Describe the steps in the formation of a synaptic junction

A

(1) the cessation of outgrowth of the axon
(2) the preparation of the nerve terminal for the ultimate release of appropriate neurotransmitter molecules
(3) modifications of the muscle fibers at the site of nerve contact so that the neural stimulus can be received and translated into a contractile stimulus

21
Q

What role does apoptosis play in the establishment of neurite and end-organ connections?

A
  • Some axons fail to reach their normal target, and cell death is a way of eliminating them.
  • Cell death could be a way of reducing the size of the neuronal pool to something appropriate to the size of the target.
  • Similarly, cell death could compensate for a presynaptic input that is too small to accommodate the neurons in question.
  • Neuronal cell death may also be a means of eliminating connection errors between the neurons and their spe- cific end organs.
22
Q

Describe the steps in the origin of sympathetic preganglionic neurons

A
  • Arise from intermediate (lateral) horns of gray matter (note similarity with the origin of somatic motor neurons from the ventral horns) – levels of origin are from T1-L2
  • Myelinated axons move through the ventral roots of the spinal cord and then through the white communicating rami
  • Preganglionic axons synapse with cell bodies of postsynaptic sympathetic motor neurons within the ganglia
23
Q

Describe the steps in the orgin of parasympathetic preganglionic neurons

A
  • Levels of origin include midbrain, hindbrain, and S2-S4
  • Those in cranial region are associated with cranial nerves III, VII, IX, and X
  • Axons of preganglionic neurons are typically long and synapse with postganglionic neurons within plexuses in or near the walls of the target organs
  • Gut wall may have considerable influence in the migratory and mitotic activity of these neurons
24
Q

What factors determine whether migrating neural crest cells differentiate into autonomic neurons or other neural crest derivatives?

A

BMPs

25
Q

What is Cholinergic differentiation factor?

A

A protein that is present in cardiomyocyte-conditioned medium, one of many chemical environmental factors that can exert a strong influence on late phases of differentiation of autonomic neurons.

26
Q

What is Hirschsprung’s Disease?

A

Absence of parasympathetic ganglia from the lower sigmoid colon and rectum, has symptoms of complete constipation without any demonstrable physical obstruction