Neural Induction and Pattern Formation

Question 1

What is the NS?

Answer 1

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

Question 2

What does the CNS do?

Answer 2

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

Question 3

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

Answer 3

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

Question 4

What are the undifferentiated regions of the embryonic brain?

Answer 4

forebrain, midbrain and hindbrain

Question 5

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

Answer 5

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

Question 6

What is neural induction?

Answer 6

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

Question 7

What coordinates patterning and regional differentiation of the NS?

Answer 7

localised signalling centres placed both outside and within the neural tube

Question 8

What do morphogen gradients do?

Answer 8

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

Question 9

How does diversity in the NS arise?

Answer 9

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

Question 10

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

Answer 10

• ectoderm
• mesoderm
• endoderm

Question 11

What is gastrulation?

Answer 11

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

Question 12

What are the 3 stages of gastrulation?

Answer 12

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

Question 13

When is the notochord formed in chordates?

Answer 13

gastrulation

Question 14

What is the notochord?

Answer 14

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

Question 15

What is a morula?

Answer 15

solid ball of cells formed as the zygote undergoes cleavage

Question 16

What is the early blastocyst?

Answer 16

a hollow ball of cells with a fluid-filled cavity

Question 17

What does the dorsal lip do?

Answer 17

organise the germ layers of the blastocyst

Question 18

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

Answer 18

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

Question 19

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

Answer 19

• epidermis when isolated prior to gastrulation
• neuron when isolated during gastrulation

Question 20

What is the animal cap?

Answer 20

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

Question 21

What can the ectoderm become?

Answer 21

skin or a neuron

Question 22

What is neurulation?

Answer 22

the making of the neural plate and neural tube

Question 23

How is the neural crest formed?

Answer 23

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

Question 24

What does neural tube closure do?

Answer 24

disconnect the neural crest from the epidermis

Question 25

What will neural crest cells eventually do?

Answer 25

form most of the PNS

Question 26

What will the neural tube eventually do?

Answer 26

become the spinal cord and brain (CNS)

Question 27

What does bone morphogenic protein 4 do?

Answer 27

inhibit neural differentiation and maintain the epithelial phenotype

Question 28

When is BMP4 first established?

Answer 28

in bone morphogenesis during development

Question 29

What are the 4 steps of the BMP pathway?

Answer 29

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

Question 30

How can the BMP signal be blocked?

Answer 30

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

Question 31

What happens when BMP signalling is blocked?

Answer 31

the ectoderm cell becomes a neuron by default

Question 32

What do mesodermal cells of the IMZ do?

Answer 32

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

Question 33

What is the general pattern of the NS determined by?

Answer 33

morphogen gradients

Question 34

How can a growth factor act?

Answer 34

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

Question 35

Where does Shh and Wnt act respectively?

Answer 35

- Shh = mesodermal (ventral) side of the developing CNS - Wnt = ectodermal (dorsal) side

Question 36

What patterns the neural cell types along the AP axis?

Answer 36

a gradient of caudalising (posterior transforming) signals

Question 37

What does a KO mouse of noggin and chordin exhibit?

Answer 37

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

Question 38

What do Hox genes do?

Answer 38

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

Question 39

What is RA derived from and what does it do?

Answer 39

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

Question 40

What is the floor plate?

Answer 40

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

Question 41

What does removal of the notochord result in?

Answer 41

loss of ventral cell types like motor neurons

Question 42

What could transplantation of the notochord generate?

Answer 42

ectopic floor plate and motor neurons

Question 43

Where are BMPs and Wnts expressed?

Answer 43

at the margin of the neural plate

Question 44

Where is Shh expressed?

Answer 44

first in the notochord and later in the floor plate

Question 45

How do Shh and Wnt signals antagonise each other?

Answer 45

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

Question 46

What is Shh?

Answer 46

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

Question 47

What does a higher concentration of Shh lead to?

Answer 47

a more ventral fate

Question 48

What does a gradient of Shh specify?

Answer 48

progenitor domains for motor neurons and four classes of spinal interneurons

Question 49

Describe Shh signalling

Answer 49

- 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