NEUROBIOLOGY LATEST 2026 TEST PAPER QUESTIONS
AND ANSWERS GRADED A+
✔✔Discovery of the Spemann-Mangold Organizer in amphibians - ✔✔Discovered by
Hilde Mangold (PhD student) and Hans Spemann (PhD advisor) in 1920-1924.
Discovered that transplanting cells from the blastopore lip of a blastula to another
embryo resulted in the formation of a second axis/nervous system in newts.
Controversy:
- Spemann took authorship credit.
- Mangold moved to Berlin and was killed soon after her work was published.
- Spemann was awarded the Nobel Prize in 1935, gave little credit to Mangold.
- This work was the foundation for our understanding of embryonic development.
✔✔The Organizer: a powerful modulator of embryonic tissue patterning - ✔✔What is it:
- piece of tissue in the blastula that can program the cells around it to eventually
become the body axis.
Where is it?
- Forms at the *dorsal blastopore lip*
Why does it form there?
- convolution of signals from the endoderm and ectoderm
How does it work?
- involutes (curls up) and becomes mesoderm
- anterior part involutes first during gastrulation and induces anterior nervous system.
- posterior part involutes later, forms posterior mesoderm, induces posterior nervous
system.
The process by which the CNS forms through interactions with underlying mesoderm is
known as *Primary Embryonic Induction*
✔✔All vertebrates have an organizer - ✔✔Called different things in different vertebrates
based on who discovered it.
SMO = Spemann-Mangold Organizer most notable.
✔✔Where is the organizer? - ✔✔The dorsal blastopore lip
- structure through which cells migrate during gastrulation.
✔✔Why does the organizer form there? - ✔✔Xenopus example (frogs)
- general set up of Xenopus blastula: organizer develops from presumptive mesoderm
between ectoderm and endoderm.
,First, mesoderm is induced by endoderm.
- removal of middle cells causes top cells to differentiate into mesoderm instead of
ectoderm.
- Then, endoderm (known as the Nieuwkoop center) induces the organizer.
✔✔How does it work? Functions of the organizer - ✔✔1. initiates movements of
gastrulation
2. Self-differentiates
3. Induces the surrounding mesoderm to form paraxial mesoderm (forms muscle and
bone precursors)
4. Induces the ectoderm to form the neural tube
✔✔How does it work? Differentiates into a signaling center - ✔✔- after involution during
gastrulation, differentiates into signaling centers.
Most notably, the notochord.
- rod of mesodermal cells.
- begins developing at 17 days in humans
- develops from organizer after gastrulation.
- gone by 7-10 weeks. Example of an embryonic tissue that undergoes programmed cell
death.
- necessary for nervous system induction and patterning.
✔✔Hensen's node (organizer) and nervous system patterning in chick and human -
✔✔Hensen's node at anterior edge of primitive streak.
Cells migrate into primitive streak during gastrulation to form germ layers.
If transplant node into new animal, induces second neural tube-primitive nervous
system.
Same thing as organizer (amphibians)
✔✔What factors does the Organizer-derived tissue produce to induce the neural
ectoderm? - ✔✔Search for factors that induce the nervous system began in the 1930s.
- Hans Holtfreter showed that if you prevent the notochord from developing, you do not
get a nervous system.
How did they know it was a diffusible factor?
- separated gastrula ectoderm and blastopore lip from newts with filter paper.
- lip contains organizer and notochord precursors.
- no cells could get through, only diffusible, secreted factors.
,First evidence that the organizer derived tissues, like the notochord, secrete something
into the environment to product the nervous system. From there, we have found various
diffusible factors.
Result: nervous system forms.
✔✔This mysterious mesodermal structure develops during gastrulation and is essential
for nervous system development. In humans, it appears at 17 days post-fertilization but
is gone by 7-10 weeks of development. - ✔✔Notochord (develops from organizer, but it
is the notochord specifically).
✔✔This tissue forms at the dorsal blastopore lip and can pattern the entire embryonic
axis - ✔✔Hensen's node (mammals), the organizer (amphibians), shield (zebrafish)
All of the above
✔✔T/F. The organizer develops into the notochord. - ✔✔T
✔✔What is the nervous system inducing factor? - ✔✔No inducing factor actually - lots of
people where looking for a specific chemical.
Inhibition of one critical factor is necessary for ectoderm to become nervous tissue.
= Bone morphogenetic protein (BMP) - inhibited factor
What is BMP?
- small protein that activates BMP receptor
- leads to phosphorylation of SMAD
- SMAD goes into nucleus and activates transcription of target genes. SMAD induces
transcription of a number of target genes that will make that cell NOT nervous system.
So if you have active BMP signaling, what will happen is that ectoderm will become just
epidermis. So if you want to make nervous system, have to have BMP inhibitors.
✔✔How does BMP impact neural induction? - ✔✔BMP is secreted by the mesoderm
and induces ectoderm to become epidermis.
BMP inhibitors from notochord and other organizer derived tissues prevent ectoderm
from becoming epidermis.
3 primary BMP inhibitors:
- Noggin
- Chordin
- Follistatin
, BMP inhibitors promote nervous system formation.
Mechanism:
- Mesoderm secretes two things: BMP and organizer derived mesoderm = notochord.
BMP turns ectoderm into epidermis (Not good!)
Notochord secretes organizer molecules like chordin, noggin, and follistatin.
- these molecules inhibit the formation of epidermis, turning ectoderm-bound cells into
neural ectoderm.
- neural ectoderm becomes the CNS.
*Need some BMP signaling so you have an epidermis, but need to inhibit a small region
of it so you still form neural ectoderm.
*Primary modulator that's giving your ectoderm the ability to become CNS is inhibitors of
BMP*
But...we know that different regions of our nervous system have different attributes...so
need some sort of specification.
✔✔How is regional specificity conferred? - ✔✔Transplantation of different regions of
gastrula to host leads to different structures.
- anterior CNS different from posterior CNS.
Signaling gradients - patterned very early on that pattern from rostral to caudal nervous
system.
✔✔Wnt signaling participates in nervous system patterning - ✔✔What is Wnt signaling?
- secreted small molecule
- binds to Wnt receptors
- activates B-catenin (transcription factor).
If Wnt signaling is "off" B catenin is degraded.
How does Wnt signaling impact neural induction?
- Wnt is active in some parts but not active in others.
- Wnt is inhibited to promote development of the anterior nervous system.
Wnt inhibitors are:
- Cerebrus, Dickkopf, Frzb, IGF. Secreted by organizer derived tissues in the anterior
mesoderm.
Wnt signaling is active in the posterior region
- no production of Wnt inhibitors in posterior mesoderm.
AND ANSWERS GRADED A+
✔✔Discovery of the Spemann-Mangold Organizer in amphibians - ✔✔Discovered by
Hilde Mangold (PhD student) and Hans Spemann (PhD advisor) in 1920-1924.
Discovered that transplanting cells from the blastopore lip of a blastula to another
embryo resulted in the formation of a second axis/nervous system in newts.
Controversy:
- Spemann took authorship credit.
- Mangold moved to Berlin and was killed soon after her work was published.
- Spemann was awarded the Nobel Prize in 1935, gave little credit to Mangold.
- This work was the foundation for our understanding of embryonic development.
✔✔The Organizer: a powerful modulator of embryonic tissue patterning - ✔✔What is it:
- piece of tissue in the blastula that can program the cells around it to eventually
become the body axis.
Where is it?
- Forms at the *dorsal blastopore lip*
Why does it form there?
- convolution of signals from the endoderm and ectoderm
How does it work?
- involutes (curls up) and becomes mesoderm
- anterior part involutes first during gastrulation and induces anterior nervous system.
- posterior part involutes later, forms posterior mesoderm, induces posterior nervous
system.
The process by which the CNS forms through interactions with underlying mesoderm is
known as *Primary Embryonic Induction*
✔✔All vertebrates have an organizer - ✔✔Called different things in different vertebrates
based on who discovered it.
SMO = Spemann-Mangold Organizer most notable.
✔✔Where is the organizer? - ✔✔The dorsal blastopore lip
- structure through which cells migrate during gastrulation.
✔✔Why does the organizer form there? - ✔✔Xenopus example (frogs)
- general set up of Xenopus blastula: organizer develops from presumptive mesoderm
between ectoderm and endoderm.
,First, mesoderm is induced by endoderm.
- removal of middle cells causes top cells to differentiate into mesoderm instead of
ectoderm.
- Then, endoderm (known as the Nieuwkoop center) induces the organizer.
✔✔How does it work? Functions of the organizer - ✔✔1. initiates movements of
gastrulation
2. Self-differentiates
3. Induces the surrounding mesoderm to form paraxial mesoderm (forms muscle and
bone precursors)
4. Induces the ectoderm to form the neural tube
✔✔How does it work? Differentiates into a signaling center - ✔✔- after involution during
gastrulation, differentiates into signaling centers.
Most notably, the notochord.
- rod of mesodermal cells.
- begins developing at 17 days in humans
- develops from organizer after gastrulation.
- gone by 7-10 weeks. Example of an embryonic tissue that undergoes programmed cell
death.
- necessary for nervous system induction and patterning.
✔✔Hensen's node (organizer) and nervous system patterning in chick and human -
✔✔Hensen's node at anterior edge of primitive streak.
Cells migrate into primitive streak during gastrulation to form germ layers.
If transplant node into new animal, induces second neural tube-primitive nervous
system.
Same thing as organizer (amphibians)
✔✔What factors does the Organizer-derived tissue produce to induce the neural
ectoderm? - ✔✔Search for factors that induce the nervous system began in the 1930s.
- Hans Holtfreter showed that if you prevent the notochord from developing, you do not
get a nervous system.
How did they know it was a diffusible factor?
- separated gastrula ectoderm and blastopore lip from newts with filter paper.
- lip contains organizer and notochord precursors.
- no cells could get through, only diffusible, secreted factors.
,First evidence that the organizer derived tissues, like the notochord, secrete something
into the environment to product the nervous system. From there, we have found various
diffusible factors.
Result: nervous system forms.
✔✔This mysterious mesodermal structure develops during gastrulation and is essential
for nervous system development. In humans, it appears at 17 days post-fertilization but
is gone by 7-10 weeks of development. - ✔✔Notochord (develops from organizer, but it
is the notochord specifically).
✔✔This tissue forms at the dorsal blastopore lip and can pattern the entire embryonic
axis - ✔✔Hensen's node (mammals), the organizer (amphibians), shield (zebrafish)
All of the above
✔✔T/F. The organizer develops into the notochord. - ✔✔T
✔✔What is the nervous system inducing factor? - ✔✔No inducing factor actually - lots of
people where looking for a specific chemical.
Inhibition of one critical factor is necessary for ectoderm to become nervous tissue.
= Bone morphogenetic protein (BMP) - inhibited factor
What is BMP?
- small protein that activates BMP receptor
- leads to phosphorylation of SMAD
- SMAD goes into nucleus and activates transcription of target genes. SMAD induces
transcription of a number of target genes that will make that cell NOT nervous system.
So if you have active BMP signaling, what will happen is that ectoderm will become just
epidermis. So if you want to make nervous system, have to have BMP inhibitors.
✔✔How does BMP impact neural induction? - ✔✔BMP is secreted by the mesoderm
and induces ectoderm to become epidermis.
BMP inhibitors from notochord and other organizer derived tissues prevent ectoderm
from becoming epidermis.
3 primary BMP inhibitors:
- Noggin
- Chordin
- Follistatin
, BMP inhibitors promote nervous system formation.
Mechanism:
- Mesoderm secretes two things: BMP and organizer derived mesoderm = notochord.
BMP turns ectoderm into epidermis (Not good!)
Notochord secretes organizer molecules like chordin, noggin, and follistatin.
- these molecules inhibit the formation of epidermis, turning ectoderm-bound cells into
neural ectoderm.
- neural ectoderm becomes the CNS.
*Need some BMP signaling so you have an epidermis, but need to inhibit a small region
of it so you still form neural ectoderm.
*Primary modulator that's giving your ectoderm the ability to become CNS is inhibitors of
BMP*
But...we know that different regions of our nervous system have different attributes...so
need some sort of specification.
✔✔How is regional specificity conferred? - ✔✔Transplantation of different regions of
gastrula to host leads to different structures.
- anterior CNS different from posterior CNS.
Signaling gradients - patterned very early on that pattern from rostral to caudal nervous
system.
✔✔Wnt signaling participates in nervous system patterning - ✔✔What is Wnt signaling?
- secreted small molecule
- binds to Wnt receptors
- activates B-catenin (transcription factor).
If Wnt signaling is "off" B catenin is degraded.
How does Wnt signaling impact neural induction?
- Wnt is active in some parts but not active in others.
- Wnt is inhibited to promote development of the anterior nervous system.
Wnt inhibitors are:
- Cerebrus, Dickkopf, Frzb, IGF. Secreted by organizer derived tissues in the anterior
mesoderm.
Wnt signaling is active in the posterior region
- no production of Wnt inhibitors in posterior mesoderm.
