Development-vonBartheld Flashcards
What is the sequence of neural development?
neural induction--> neural tube formation--> generation of neurons & glia--> axon growth from neurons--> synapses made with targets--> dendrite growth--> myelination
How do you get the 3 germ layers developmentally?
epiblast cells invaginate thru the primitive streak.
Then you get ectoderm, mesoderm, and endoderm
Describe the basic sequence of neurlation (neural tube formation).
ectoderm thickens in the middle & forms a neural plate
then you get a neural groove
the dorsal edges align & fuse–>get a neural tube!
Note: the neural tube first forms in the central part (from bird’s eye view) & then zips caudally & rostrally.
Somites form on either side.
By day 23, caudal & cranial neuropores have formed.
By day 26, neurelation is complete.
What induces the ectoderm to become a neural plate?
this induction happens via the notochord underneath the ectoderm.
What is the equivalent of the notochord in amphibians? This was used in experiments to figure out the role of the notochord in neural plate induction.
the equivalent is the organizer in the dorsal region of the amphibians.
What does an organizer usu do in an amphibian?
generates axial mesoderm during normal development.
Who dated Hans Spemann?
von Bartheld’s grandfather’s sister. : )
What is the default fate of the ectoderm? What stops this?
Default: become neuronal
BMP4 inhibits this.
T/F In addition to BMP4, there are a large number of molecules that regulate different parts of the neural tube.
True.
T/F Different transcription factors code for different parts of the neural tubes.
True.
Where are neurons generated developmentally?
they are generated in the ventricular zone
the ventricular zone is made of the neuroepithelial layer that borders the neural tube.
When does neural tube closure happen? What is the clinical significance of this?
early 4th week
so a woman could be 22 days pregnant w/o even knowing it…then she could have the problem of teratogens affecting the neural formation of her baby.
What is spina bifida occulta?
this happens when the vertebral arches of the bone don’t form properly.
happens in up to 5% of the population
What is a meningocele?
this happens with prolapse of the subarachnoid space
this can happen at the spinal or cranial level
even tho the neural tube is still intact, you need surgery.
What is a meningomyocele?
this is where the spinal cord is prolapsed into outer space, white matter may be protruding
What is rachischisis (no fold & fold)?
this is where you have no neural tube
the neural tissue that is overlying can be folded or not
What is a clinical sign of spina bifida occulta?
tufts of hair on lower back
What are 2 tragic neural tube defects that are not compatible with life?
cranial meningomyelocele
anencephaly
T/F Pts with anencephaly don’t have any brain structures.
False. They don’t have a telencephalon. They do have a brainstem, and thus can be born & live for several days.
What is the most common human malformation?
neural tube defects
What is the incidence of NTDs?
1-8/1000 live births
**incidence has been more recently reduced b/c of abortions after detection of NTD
What is the etiology of NTD?
failure of the neural tube to close
What is the cause of NTD?
multifactorial
could be chromosomal, diabetes, teratogens, hyperthermia
What types of meds should you NOT take if you are pregnant (capable of causing NTDs)?
epilepsy meds acne meds (Vit A high)
What are some things that can help in detection of NTDs?
ultrasound (detects anencephaly especially)
alpha fetoprotein
What is something that helps in prevents of NTDs?
folic acid!
-this has a 72% reduction power in incidence of NTDs
now we have fortified flour w/ folic acid in it etc.
-prevents 30 - 50% of NTDs
What is a problem with fortifying our food supply with folic acid?
main issue is that if a pt has Vit B12 deficiency, the folate they are taking will mask the symptoms (hematologic disease) & will worsen the neurological symptoms
What are 3 classes of teratogens affecting neuronal development?
infectious agents
physical agents/temp
drugs
What are some of the infectious agent teratogens? What are their effects?
rubella-eye & ear defects
cytomegalovirus-eye defect, microcephaly
toxoplasmosis-hydrocephalus
Where do you find taxoplasmosis?
you find it in cat litter
it is a parasite
What are some physical agents that are teratogens? What are their effects?
X-rays–spina bifida occulta
hyperthermia–NTD
What are some drugs that are teratogens? What are their effects?
Epilepsy meds-NTD
Vit A overdose/acne meds-NTD
folic acid antagonists-NTD
alcohol-MR
There is a risk of which malformation of the fetus during weeks 0-3 in utero?
death of embryo may occur
There is a risk of which malformation of the fetus during weeks 3-8 in utero? What happens during this time frame?
risk of malformation of the embryo-esp heart defects
**maximally sensitive during this period
There is a risk of which malformation of the fetus during weeks 8-birth in utero? What happens during this time frame?
functional disturbance of the fetus, such as MR
during this time get growth & maturation of organ systems
What are some of the signs of FAS?
thin upper lip short palpebral fissure flat nasal bridge short nose elongated philtrum
Describe the development of the placode & neural tube from the eye.
optic grooves form and then become optic vesicles.
overlying ectoderm becomes a lens placode
they both end up invaginating
The optic cup is connected to which structure?
optic stalk
The lumen of the optic stalk leads to which space?
intraretinal space
Which artery goes toward the lens placode?
hyaloid artery
If you took a cross section of the optic stalk what would it show?
an outer layer & inner layer with a lumen in b/w
a hyaloid artery deep to the inner layer
and a choroid fissure that separates the 2 sides from making a tube
If this choroid fissure remains…what happens? How common is this disease?
you get MAC disease
microphthalmia, anophthalmia, coloboma
***1/10000
Describe the components of the eye in 7 week embryo.
the globe is in undifferentiated mesenchyme
ectoderm is on the outer surface
optic nerve fibers enter with a hyaloid vessel
there are also lens fibers & an anterior lens epithelium
there is an inner neural layer & an outer pigment layer of the retina
What all happens with retinal detachment?
the inner layer of the retina peels off
Describe the beginning steps of the formation of the inner ear.
Otic placode formed from ectoderm
the placode invaginates
it makes an otic pit
it makes an otic vesicle
What happens to the epithelium in the otic vesicle?
it forms the statoacoustic ganglion (this lies next to the vesicle)
What are the 2 sources of the tissue that composes the statoacoustic ganglion?
most comes from the otic placode
other parts come from neural crest cells
**none comes from neural tube
Past the part that we have discussed, describe the formation of the inner ear.
Endolymphatic sac connects to endolymphatic duct
utricular portion of otic vesicle
goes to utriculosaccular duct
goes to saccular portion of otic vesicle
**then a tubular outgrowth of saccule happens & makes a swirl & forms the cochlear duct
Describe the development of the canal of the inner ear.
you get flattened out pocketing of the utricle
get apposition of walls of opposing outpocketings
walls disappear & you get semicircular canals
What is the middle ear derived from?
endoderm-tympanic cavity
1st & 2nd pharyngeal arches–ossicles
Which types of genes regulate segmentation of the neuraxis?
Hox Genes
T/F Hox genes are expressed in certain segments. If you misexpress them, you can change their fate.
True.
Describe neural tube & ventricular development.
the lateral ventricles are significantly altered, but not the third ventricle
**Prosencephalon–>Telencephalon + Diencephalon
Mesencephalon remains.
Rhombencephalon–>Metencephalon + Myelencephalon
Spinal cord remains.
If you peel away the cerebellum what are you left with?
a rhombus! Why it is called the rhombencephalon
If you get a stenosis of the cerebral aqueduct, what condition do you develop?
hydrocephalus
What are the 2 embryonic origins of the pituitary gland?
anterior lobe: ectoderm
posterior lobe: neural tube
T/F Rathke’s pouch extends into the area of the diencephalon.
True. Note: rathke’s pouch gives rise to the adenohypophysis
Where is a safe place to do a lumbar puncture?
L3/L4 you won’t hit spinal cord
Describe spinal cord/vertebrae development.
at first the spinal cord grows much faster than the vertebrae
3 months in utero: have more spinal cord
but the vertebrae eventually catch up & outgrow in length
What are the sources of neurons & glia?
neural tube (ventricular zone)
placodes
neural crest
stem cells
Describe the process of neurogenesis in a ventricular zone.
cell’s axons extend from the ventricular zone to the marginal zone.
the cell body starts on one side & then becomes closer to the marginal side & then moves back down again. Then it loses its processes that contact the zones. It divides into 2 daughter cells. Then the daughter cell gets a process to each zone. This cycles until there are sufficient glioblasts
Describe neural crest migration.
the upper portion of the tube has neural crest cells
these migrate along different pathways & attain different fates
they become mesenchymal cells, b/c this is what you must be to migrate.
What are some of the different things that neural crest cells can become?
pigment cells in skin DRG or sympathetic ganglion adrenal gland some sort of plexus chromaffin cells in adrenal medulla multipolar neuron schwann cell satellite cell
T/F Neural crest cells have a huge role in forming the back.
False. The face.
The neural crest cells of the trunk crest makes spinal ganglia, and the cranial crest makes what?
cranial ganglia (5, 7, 9, 10)
The neural crest cells of the cranial crest makes parasympathetic ganglia, but the trunk crest makes what?
sympathetic ganglia
The neural crest cells of the trunk crest makes glial cells of peripheral nerves, but the cranial crest makes what?
glial cells of peripheral nerves & leptomeninges
T/F Both neural crest cells of the trunk crest & cranial crest make melanocytes.
True.
T/F Neural crest cells of the cranial chest make the adrenal medulla.
False. Of the trunk crest
What are some other structures that neural crest cells of the cranial crest form?
carotid body thyroid skeleton (cranial bone & cartilage) CT (dermis, odontoblasts) Muscle (ciliary & vascular)
What is an embryonic stem cell?
- self-renewing; can give rise to ALL tissue and cell types (including germ cells)
What is a somatic stem cell?
- Self-renewing
- Can give rise to full range of diploid, tissue-specific cell classes
What is a neural stem cell?
- self-renewing
- can give rise to any diploid cell type in the CNS or PNS
What is a neural progenitor cell?
- no self-renewal; can give rise to only one class of neurons
What type of cells are microglia made from?
a type of mesenchymal cell that migrates into the brain
How can you make a multipolar neuroblast?
a neuroepithelial cell–>
bipolar neuroblast–>
multipolar neuroblast
How do you get a protoplasmic astrocyte?
a neuroepithelial cell–>
gliablast–>
protoplasmic astrocyte
How do you get a fibrillar astrocyte?
a neuroepithelial cell–>
gliablast–>
fibrillar astrocyte
How do you get oligodendroglia?
a neuroepithelial cell–>
gliablast–>
olgodendroglia
How do you get an ependymal cell?
from a neuroepithelial cell
Schwann cells myelinate axons located where?
located in the periphery
Which type of cell myelinates axons in the CNS? Note: one of these cells myelinates a bunch of axons.
oligodendrocytes
What are the 2 theories of how we get cellular diversity?
Lineage Theory & Environment Theory
Describe the theory of cell lineage for cellular diversity.
an uncommitted precursor cleaves
second cleavage produces diversity of daughter cells
lineage leads to diversity in daughter cells
**cells acquire diverse fates at the precursor state
rely on information intrinsic to the cell
Describe the theory of environment for cellular diversity.
uncommitted precursor
cleaves to form uncommitted daughter exposed to environmental signals, intercellular signals
signaling leads to diversity in daughter cells
**pleuropotential precursor, diversity generated among daughter cells from specific signals from other cells
T/F Different signalling molecules turn neural crest progenitors into different phenotypes. Ex: Neural crest progenitor–>melanocyte via stem cell factor
True.
Which factors allow you to go from neural crest progenitor to chromaffin cell?
glucocorticoids!
Which factors allow you to go from neural crest progenitor to sensory neuron?
LIF: leukocyte initiating factor
Which factors allow you to go from neural crest progenitor cell to adrenergic or cholinergic neurons?
Neural crest–>sympathetic progenitor via FGF2
Sympathetic Progenitor–>Adrenergic Neuron via NGF
Sympathetic Progenitor–>Cholinergic Neuron via Ciliary Neurotrophic Factor
How do you generate a cortex?
by moving neurons from the ventricular zone to the cortex (plial surface) via radial glial processes
Describe the inside out layer of the cortex.
studies have shown thru radioactive data
earliest neurons born are in the white matter
latest neurons born are in the cortex
Should you get a 4 hour 4D ultrasound for your baby?
NO
Give some examples of neuronal migration.
Neural Crest
Mesencephalic nucleus of the trigeminal nerve
Olfactory placode/hypothalamus: GnRH neurons
Oculomotor neurons: exchange across the midline
