Patterning the brain Flashcards
what are the major divisions of the vertebrate brain?
- forebrain
- midbrain
- hindbrain
- cerebellum
what happens during brain development with respect to the neural plate?
- during brain development, the regions of the neural plate are already patterned, and it undergoes neurulation to form three brain vesicles
what are the key developmental processes involved in brain development?
- brain development involves pattern formation, growth, differentiation, and morphogenesis
what is the role of morphogens in brain development?
- 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).
What are the 2 steps of pattern formation during brain development?
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
What are local signals in pattern formation?
local signals in pattern formation involve cell-to-cell communication
what are long-range signals in pattern formation?
- long-signals in pattern formation come from a distance & often referred to as morphogens
- provide positional information to cells in developing group
What is the french flag model in pattern formation?
- 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
What does the organizer secrete during anterior-posterior patterning from gastrula to neural plate?
BMP antagonists
What does the BMP antagonists do in the neural tissue during anterior-posterior patterning?
- 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.
What structures involute through the organizer during anterior-posterior patterning from gastrula to neural plate?
A sheet of endoderm and mesoderm
What is the outcome of the first involuted sheet (possibly mesoderm) passing through the organizer?
- releases signals that induce the formation of anterior neural tissue in the neural ectoderm
What is the outcome of the second involuted sheet during anterior-posterior patterning from gastrula to neural plate?
It induces the formation of the posterior part of the neural tube
Why are BMP antagonists secreted by the organizer important for neural tissue specification?
- 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.
What signal promotes neural and anterior tissue in the ectoderm during development?
BMP antagonists (e.g., chordin) from the organizer (dorsal mesoderm)
What is induced by BMP antagonists in the neural tissue during development?
Otx2 (TF) expression
In what pattern are the antagonists expressed?
In a gradient pattern in all directions
After neural induction, which signalling molecules are required for patterning?
Wnt and BMP
What does the Wnt signalling pattern posteriorly, and what does BMP signalling pattern?
Wnt patterns posteriorly;
BMP patterns ventrally
What fates form in the gradient of Wnt signalling?
Spinal cord, hindbrain, midbrain, forebrain (from high to low Wnt gradient)
What happens if Wnt signalling is lost or increased during development?
- Loss of Wnt signalling leads to larger forebrain structures;
- increased Wnt leads to increased spinal cord development but less brain formation
What is retinoic acid (RA), and what is its role during development?
- Retinoic acid is a derivative of Vitamin A, and it is required for posterior specification during development
Where is retinoic acid expressed in the neurula stage, and in what pattern?
Retinoic acid is expressed in the posterior mesoderm in a gradient pattern
What happens when the concentration of retinoic acid increases during development?
- 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.
What determines the formation of signalling centres in the anterior brain during development?
Neural plate TF expression
What is the isthmus organiser, and how is it formed?
- the isthmus organiser is where Otx2 and Gbx2 meet and cross-repress each other, forming a sharp boundary.
What happens if Otx2 or Gbx2 is knocked out during development?
Otx2 knockout leads to no brain anterior to the hindbrain, while Gbx2 knockout leads to no hindbrain formation
Which signalling molecules are required to pattern the region of the isthmus organiser?
FGF8 and Wnt1 expression are required.
What happens if FGF8 is knocked out during development?
Knockout of FGF8 leads to no midbrain and cerebellum formation
What happens if Wnt1 is knocked out in the isthmus organiser during development?
Knockout of Wnt1 in the isthmus leads to no cerebellum or midbrain formation
What is the function of the isthmus organiser during development?
- The isthmus organiser is an organizing region required for patterning the cerebellum (anterior hindbrain) and midbrain
What happens if the isthmus from a quail embryo is transplanted more anteriorly into a chick embryo?
- Extra isthmus forms in the forebrain, leading to the development of extra midbrain and cerebellum.
What happens if the isthmus from a quail embryo is transplanted more anteriorly into a chick embryo?
what is the ZLI (Zona Limitans Intrathalamica) in brain development?
- specific boundary region located in the diencephalon of the developing brain
- plays a crucial role in patterning the forebrain and midbrain
What does “patterning of the ZLI” refer to in brain development?
- 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.
What forms when Six3 and Irx3 meet during development?
The ZLI (Zona Limitans Intrathalamica)
Where does the ANR (anterior neural ridge) form, and what is its role in brain development?
ANR forms at the anterior neural border (ANB) and is required for forebrain patterning
Which transcription factors are expressed in the dorsal and ventral forebrain?
Emx is expressed in the dorsal forebrain, and Dlx is expressed in the ventral forebrain
What happens if the ANR is removed during development?
- 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
What does SFRP (secreted frizzled related protein) do during brain development?
SFRP acts as a Wnt antagonist, binding to Wnt and preventing it from binding to its receptor
What is the role of SFRP (tlc) expressed in row 1 of the ANB?
SFRP induces telencephalic (forebrain) markers.
What is the hindbrain segmented into during brain development?
rhombomeres
What are “rhombomeres”?
- 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
What defines the boundaries of rhombomeres in the hindbrain?
- 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
What is the role of Hox genes in the patterning of the hindbrain? Give experimental evidence for answer
- 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
What does the notochord become during brain development, and what does it induce above it?
- 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
What happens if the notochord is removed during brain development?
- 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.
What signaling molecule is present in the notochord and floor plate? and what crucial role does it play?
- 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
What are Class 1 and Class 2 transcription factors?
= Class 1 and Class 2 transcription factors are two distinct classes of regulatory proteins expressed in the developing spinal cord
How does Shh signaling influence Class 1 and Class 2 transcription factors?
- Shh signaling, emanating from the floor plate, activates Class 2 proteins & represses Class 1 proteins in the developing spinal cord.
What is the outcome of the cross-repressive interaction between Class 1 and Class 2 transcription factors?
- the cross-repressive interaction between Class 1 and Class 2 transcription factors helps establish boundaries between different types of neurons in the spinal cord
How does the interaction between Class 1 and Class 2 transcription factors contribute to neuronal diversity?
- this interaction leads to the formation of diverse neuronal subtypes with distinct functions and properties within the developing spinal cord
When does most patterning occur in neural tube development?
Most patterning occurs early after the closure of the neural tube.
How is cell identity refined during neural tube development?
- through local changes in positional information received from nearby signalling centres
What happens when patterning decisions are made during neural tube development?
Patterning decisions are locked, and signalling becomes restricted to specific directions
- leading to the formation of segments and boundaries.
