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5BBA2300 Essentials of Embryology > Patterning the brain > Flashcards

Patterning the brain Flashcards

1
Q

what are the major divisions of the vertebrate brain?

A
  • forebrain
  • midbrain
  • hindbrain
  • cerebellum
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2
Q

what happens during brain development with respect to the neural plate?

A
  • during brain development, the regions of the neural plate are already patterned, and it undergoes neurulation to form three brain vesicles
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3
Q

what are the key developmental processes involved in brain development?

A
  • brain development involves pattern formation, growth, differentiation, and morphogenesis
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4
Q

what is the role of morphogens in brain development?

A
  • morphogens are signaling molecules that give positional values and identity during brain development.
  • they come from two signaling centers: the anterior neural ridge (ANR) and the midbrain-hindbrain boundary (MHB).
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5
Q

What are the 2 steps of pattern formation during brain development?

A

two steps of pattern formation
1. Cells obtain unique positional information by receiving specific signals (local or long-range)
2. Cells interpret this positional information to express specific genes

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6
Q

What are local signals in pattern formation?

A

local signals in pattern formation involve cell-to-cell communication

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7
Q

what are long-range signals in pattern formation?

A
  • long-signals in pattern formation come from a distance & often referred to as morphogens
  • provide positional information to cells in developing group
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8
Q

What is the french flag model in pattern formation?

A
  • ccells acquire positional identity depending on position in morphogen grad (relative to signalling centre)
  • cells then express specific TFs ⟶ specific cell fates
  • NOTE: patterns are generated from grad of expression, ensuring each cell is in the right place
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9
Q

What does the organizer secrete during anterior-posterior patterning from gastrula to neural plate?

A

BMP antagonists

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10
Q

What does the BMP antagonists do in the neural tissue during anterior-posterior patterning?

A
  • Inhibit BMP signaling in the neural tissue adjacent to the organizer, allowing the development of neural tissue.
  • Further away in the epidermis, BMP signaling is not inhibited.
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11
Q

What structures involute through the organizer during anterior-posterior patterning from gastrula to neural plate?

A

A sheet of endoderm and mesoderm

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12
Q

What is the outcome of the first involuted sheet (possibly mesoderm) passing through the organizer?

A
  • releases signals that induce the formation of anterior neural tissue in the neural ectoderm
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13
Q

What is the outcome of the second involuted sheet during anterior-posterior patterning from gastrula to neural plate?

A

It induces the formation of the posterior part of the neural tube

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14
Q

Why are BMP antagonists secreted by the organizer important for neural tissue specification?

A
  • BMP antagonists prevent BMP signaling in the adjacent neural tissue, allowing it to develop into neural tissue
  • Without BMP inhibition, the tissue would develop into non-neural ectoderm.
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15
Q

What signal promotes neural and anterior tissue in the ectoderm during development?

A

BMP antagonists (e.g., chordin) from the organizer (dorsal mesoderm)

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16
Q

What is induced by BMP antagonists in the neural tissue during development?

A

Otx2 (TF) expression

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17
Q

In what pattern are the antagonists expressed?

A

In a gradient pattern in all directions

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18
Q

After neural induction, which signalling molecules are required for patterning?

A

Wnt and BMP

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19
Q

What does the Wnt signalling pattern posteriorly, and what does BMP signalling pattern?

A

Wnt patterns posteriorly;
BMP patterns ventrally

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20
Q

What fates form in the gradient of Wnt signalling?

A

Spinal cord, hindbrain, midbrain, forebrain (from high to low Wnt gradient)

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21
Q

What happens if Wnt signalling is lost or increased during development?

A
  • Loss of Wnt signalling leads to larger forebrain structures;
  • increased Wnt leads to increased spinal cord development but less brain formation
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22
Q

What is retinoic acid (RA), and what is its role during development?

A
  • Retinoic acid is a derivative of Vitamin A, and it is required for posterior specification during development
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23
Q

Where is retinoic acid expressed in the neurula stage, and in what pattern?

A

Retinoic acid is expressed in the posterior mesoderm in a gradient pattern

24
Q

What happens when the concentration of retinoic acid increases during development?

A
  • at increasing concentrations of retinoic acid, the forebrain and midbrain are lost at low concentrations & the hindbrain is lost at high concentrations, leaving only the spinal cord.
25
Q

What determines the formation of signalling centres in the anterior brain during development?

A

Neural plate TF expression

26
Q

What is the isthmus organiser, and how is it formed?

A
  • the isthmus organiser is where Otx2 and Gbx2 meet and cross-repress each other, forming a sharp boundary.
27
Q

What happens if Otx2 or Gbx2 is knocked out during development?

A

Otx2 knockout leads to no brain anterior to the hindbrain, while Gbx2 knockout leads to no hindbrain formation

28
Q

Which signalling molecules are required to pattern the region of the isthmus organiser?

A

FGF8 and Wnt1 expression are required.

29
Q

What happens if FGF8 is knocked out during development?

A

Knockout of FGF8 leads to no midbrain and cerebellum formation

30
Q

What happens if Wnt1 is knocked out in the isthmus organiser during development?

A

Knockout of Wnt1 in the isthmus leads to no cerebellum or midbrain formation

31
Q

What is the function of the isthmus organiser during development?

A
  • The isthmus organiser is an organizing region required for patterning the cerebellum (anterior hindbrain) and midbrain
32
Q

What happens if the isthmus from a quail embryo is transplanted more anteriorly into a chick embryo?

A
  • Extra isthmus forms in the forebrain, leading to the development of extra midbrain and cerebellum.
33
Q

What happens if the isthmus from a quail embryo is transplanted more anteriorly into a chick embryo?

A
34
Q

what is the ZLI (Zona Limitans Intrathalamica) in brain development?

A
  • specific boundary region located in the diencephalon of the developing brain
  • plays a crucial role in patterning the forebrain and midbrain
35
Q

What does “patterning of the ZLI” refer to in brain development?

A
  • process by which the boundaries of this specific region in the brain are established and defined during development
  • involves interaction of specific TFs such as Six3 and Irx3, to determine identity & positional values of cells within ZLI.
36
Q

What forms when Six3 and Irx3 meet during development?

A

The ZLI (Zona Limitans Intrathalamica)

37
Q

Where does the ANR (anterior neural ridge) form, and what is its role in brain development?

A

ANR forms at the anterior neural border (ANB) and is required for forebrain patterning

38
Q

Which transcription factors are expressed in the dorsal and ventral forebrain?

A

Emx is expressed in the dorsal forebrain, and Dlx is expressed in the ventral forebrain

39
Q

What happens if the ANR is removed during development?

A
  • removing ANR leads to the loss of emx expression in the dorsal forebrain, and some dlx expression remains in the ventral forebrain, mainly in the diencephalon
40
Q

What does SFRP (secreted frizzled related protein) do during brain development?

A

SFRP acts as a Wnt antagonist, binding to Wnt and preventing it from binding to its receptor

41
Q

What is the role of SFRP (tlc) expressed in row 1 of the ANB?

A

SFRP induces telencephalic (forebrain) markers.

42
Q

What is the hindbrain segmented into during brain development?

A

rhombomeres

43
Q

What are “rhombomeres”?

A
  • cell-tight compartments within which neural precursors acquire their positional identity
  • they play a crucial role in patterning & organizing motor neurons that pattern the PNS
44
Q

What defines the boundaries of rhombomeres in the hindbrain?

A
  • by the expression of Homeobox proteins [known as “Hox genes.”]
  • Hox gene expression respects the rhombomere boundaries
  • each rhombomere characterized by unique combination of Hox gene expression, providing positional identity to the neurons within each compartment
45
Q

What is the role of Hox genes in the patterning of the hindbrain? Give experimental evidence for answer

A
  • play a critical role in determining the positional identity of rhombomeres and the neurons within them
  • Experimental manipulations, such as over-expressing a specific Hox gene (e.g., Hoxb1) in different rhombomere (e.g., R2), can transform identity of that rhombomere to that of the Hox gene normally expressed in the target rhombomere (e.g., R4)
  • provides evidence that Hox genes are responsible for controlling the positional identity and patterning of the hindbrain
46
Q

What does the notochord become during brain development, and what does it induce above it?

A
  • notochord elongates under the neural plate during brain development and becomes a vital signaling center
  • acts as an organizer and induces formation of the “floor plate” above it
  • floor plate is essential for generating motor neurons in the developing brain
47
Q

What happens if the notochord is removed during brain development?

A
  • experimental removal of notochord leads to the absence of the floor plate and motor neurons in the developing brain
  • demonstrates that notochord plays crucial role in inducing the floor plate - which, in turn, is responsible for the generation of motor neurons.
48
Q

What signaling molecule is present in the notochord and floor plate? and what crucial role does it play?

A
  • Shh (Sonic Hedgehog) is a secreted signaling molecule that exhibits a ventral-to-dorsal gradient in the ventral neural tube
  • expressed in both the notochord and floor plate
  • plays crucial role in patterning and specifying cell fates along the ventral-dorsal axis of the developing brain
49
Q

What are Class 1 and Class 2 transcription factors?

A

= Class 1 and Class 2 transcription factors are two distinct classes of regulatory proteins expressed in the developing spinal cord

50
Q

How does Shh signaling influence Class 1 and Class 2 transcription factors?

A
  • Shh signaling, emanating from the floor plate, activates Class 2 proteins & represses Class 1 proteins in the developing spinal cord.
51
Q

What is the outcome of the cross-repressive interaction between Class 1 and Class 2 transcription factors?

A
  • the cross-repressive interaction between Class 1 and Class 2 transcription factors helps establish boundaries between different types of neurons in the spinal cord
52
Q

How does the interaction between Class 1 and Class 2 transcription factors contribute to neuronal diversity?

A
  • this interaction leads to the formation of diverse neuronal subtypes with distinct functions and properties within the developing spinal cord
53
Q

When does most patterning occur in neural tube development?

A

Most patterning occurs early after the closure of the neural tube.

54
Q

How is cell identity refined during neural tube development?

A
  • through local changes in positional information received from nearby signalling centres
55
Q

What happens when patterning decisions are made during neural tube development?

A

Patterning decisions are locked, and signalling becomes restricted to specific directions
- leading to the formation of segments and boundaries.

5BBA2300 Essentials of Embryology (12 decks)

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