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Neuro Development and Disease > Neural Induction and Pattern Formation > Flashcards

Neural Induction and Pattern Formation Flashcards

1
Q

What is the NS?

A

a group of specialised cells responsible for sensing the internal and external environment

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2
Q

What does the CNS do?

A

transmit electrochemical messages to organs and tissues that initiate and appropriate response

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3
Q

Give examples of organisms that have alternative structures in place of a brain

A
  • hydra (cnidarian) have nerve nets
  • starfish have ganglia to produce integration
  • flatworms have 2 longitudinal nerve cords
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4
Q

What are the undifferentiated regions of the embryonic brain?

A

forebrain, midbrain and hindbrain

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5
Q

What do the forebrain, midbrain and hindbrain develop into respectively?

A
  • forebrain = telencephalon (cerebrum) and diencephalon
  • midbrain = mesencephalon
  • hindbrain = pons and medulla oblongata
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6
Q

What is neural induction?

A

the development of the CNS from an epithelial plate of ectoderm cells triggered by molecular signals from the early midline mesoderm

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7
Q

What coordinates patterning and regional differentiation of the NS?

A

localised signalling centres placed both outside and within the neural tube

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8
Q

What do morphogen gradients do?

A

generate discrete changes in the populations of TFs expressed by individual cells

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9
Q

How does diversity in the NS arise?

A

from the action of a small set of morphogen families expressed in the fight place at the right time e.g. Shh, retinoic acid (RA), Wnts, BMPs/TGFbs and FGFs

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10
Q

What are the 3 primary germ layers that give rise to all adult tissues during gastrulation?

A
  • ectoderm
  • mesoderm
  • endoderm
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11
Q

What is gastrulation?

A

the process by which an embryo transforms from a one-dimensional layer of epithelial cells (blastula) and reorganises into a multi-layered and multidimensional structure called the gastrula

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12
Q

What are the 3 stages of gastrulation?

A
  1. prospective endoderm is brought inside the embryo
  2. prospective ectoderm covers the surface of the embryo
  3. prospective mesoderm is positioned between the 2 layers
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13
Q

When is the notochord formed in chordates?

A

gastrulation

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14
Q

What is the notochord?

A

a flexible rod-like structure of mesodermal cells that is the principal longitudinal structural element

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15
Q

What is a morula?

A

solid ball of cells formed as the zygote undergoes cleavage

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16
Q

What is the early blastocyst?

A

a hollow ball of cells with a fluid-filled cavity

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17
Q

What does the dorsal lip do?

A

organise the germ layers of the blastocyst

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18
Q

What shows the dorsal lip’s sufficiency in neural induction?

A

when transplanted, it can induce formation of a double axis in the new host embryo

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19
Q

When will an isolated animal cap differentiate into epidermis and neurons respectively?

A
  • epidermis when isolated prior to gastrulation
  • neuron when isolated during gastrulation
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20
Q

What is the animal cap?

A

a region of the Xenopus blastula and early gastrula stage embryo that forms the roof of the upper, pigmented half of egg/embryo

21
Q

What can the ectoderm become?

A

skin or a neuron

22
Q

What is neurulation?

A

the making of the neural plate and neural tube

23
Q

How is the neural crest formed?

A
  1. the notochord induces neuroectodermal differentiation from the ectoderm
  2. ectoderm thickens to form the neural plate
  3. neural plate folds in dorsally to form the neural tube
  4. the 2 ends of the neural tube eventually join to form the neural crest
24
Q

What does neural tube closure do?

A

disconnect the neural crest from the epidermis

25
Q

What will neural crest cells eventually do?

A

form most of the PNS

26
Q

What will the neural tube eventually do?

A

become the spinal cord and brain (CNS)

27
Q

What does bone morphogenic protein 4 do?

A

inhibit neural differentiation and maintain the epithelial phenotype

28
Q

When is BMP4 first established?

A

in bone morphogenesis during development

29
Q

What are the 4 steps of the BMP pathway?

A
  1. BMP ligands bind to the BMP receptors 1 and 2 to form a receptor complex
  2. BMPR2 phosphorylates and activates BMPR1
  3. phosphorylated BMPR1 phosphorylates SMAD1, 5 and 8 which associate with SMAD4 (cofactor) and enter the nucleus
  4. the SMAD complex acts as TFs to regulate gene expression
30
Q

How can the BMP signal be blocked?

A

by extracellular antagonists, such as noggin, which bind BMP ligands and prevent their association with the BMP receptors

31
Q

What happens when BMP signalling is blocked?

A

the ectoderm cell becomes a neuron by default

32
Q

What do mesodermal cells of the IMZ do?

A

release BMP antagonists like noggin, chordin and follistatin that drive neuroectoderm formation

33
Q

What is the general pattern of the NS determined by?

A

morphogen gradients

34
Q

How can a growth factor act?

A
  • instructively (specifically activate genes required for the development
  • selectively (promotes the survival of cells that already express specific properties)
35
Q

Where does Shh and Wnt act respectively?

A
  • Shh = mesodermal (ventral) side of the developing CNS
  • Wnt = ectodermal (dorsal) side
36
Q

What patterns the neural cell types along the AP axis?

A

a gradient of caudalising (posterior transforming) signals

37
Q

What does a KO mouse of noggin and chordin exhibit?

A

extensive anterior deletions of forebrain, eye, nose and facial structures and the posterior structures are present but defective

38
Q

What do Hox genes do?

A

produce TFs that determine type of structures that develop along the AP axis

39
Q

What is RA derived from and what does it do?

A

retinol (vitamin A) and acts as ligand for nuclear RA receptors (RARs), converting them from transcriptional repressors to activators

40
Q

What is the floor plate?

A

a specialised glial structure that spans the AP axis from the midbrain to the tail regions

41
Q

What does removal of the notochord result in?

A

loss of ventral cell types like motor neurons

42
Q

What could transplantation of the notochord generate?

A

ectopic floor plate and motor neurons

43
Q

Where are BMPs and Wnts expressed?

A

at the margin of the neural plate

44
Q

Where is Shh expressed?

A

first in the notochord and later in the floor plate

45
Q

How do Shh and Wnt signals antagonise each other?

A

by setting up opposite gradients that determine the dorsal, ventral and intermediate cell fates

46
Q

What is Shh?

A

a morphogen that determines how the early CNS is patterned along the DV axis

47
Q

What does a higher concentration of Shh lead to?

A

a more ventral fate

48
Q

What does a gradient of Shh specify?

A

progenitor domains for motor neurons and four classes of spinal interneurons

49
Q

Describe Shh signalling

A
  • in the absence of Shh, the system is an “off” state and the GLI TFs in the primary cilium are processed into transcriptional repressors
  • binding of Shh to its receptor Patched1 (PTCH1) relieves Smoothened (SMO) inhibition by PTCH1 and activates the pathway (“on” state) and the GLI factors are then processed into transcriptional activators

Neuro Development and Disease (9 decks)

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