Ectodermal Derivatives Flashcards
(110 cards)
1
Q
When does organogenesis occur? And what stage does it follow?
A
Organogenesis extends from the end of week 3 until week 8, signifying the end of the gastrulation stage.
2
Q
What is supposed to happen by the end of the second month of development?
A
The embryonic period must end, and the major features of the external body must be recognizable.
3
Q
In which species is Wnt seen? Name a few.
A
Nearly all species, including C. elegans, tunicates, drosophila, mammals, and amphibians.
4
Q
Briefly, what are the major derivatives of the ectoderm germ layer?
A
Epidermis, Neural Crest, and Neural Plate (Neural Tube) cells.
5
Q
What happens if the ectoderm is exposed to high levels of BMP?
A
Differentiates into epidermal derivatives.
6
Q
What happens if the ectoderm is exposed to moderate levels of BMP with high Wnt?
A
Differentiates into neural crest derivatives.
7
Q
What happens if the ectoderm is exposed to low levels of BMP?
A
Differentiates into neural plate cells if SOX TFs are present.
8
Q
Are low levels of BMP sufficient for neural plate formation?
A
Low BMP levels are necessary but not sufficient for neural plate formation. SOX TFs must also be present, else the cells remain unprogrammed or have epidermal fates.
9
Q
What are the epidermal derivatives?
A
Epidermis, hair, nails, sebaceous glands, olfactory epithelium, lens, cornea, and mouth epithelium — anterior pituitary, tooth enamel, and cheek epithelium.
10
Q
What are the neural crest derivatives?
A
Mainly the peripheral nervous system (PNS), including Schwann cells, glial cells, SNS, and PSNS cells. Also include adrenal medulla, melanocytes, facial cartilage, and dentine of teeth.
11
Q
What are the neural plate derivatives?
A
Mainly the central nervous system (CNS), including the brain, spinal cord, meninges, motor neurons, and retina.
12
Q
Briefly, what is primary neurulation? What about secondary neurulation? Which ectodermal derivative does it involve?
A
During primary neurulation, neural plate cells proliferate, invaginate, and pinch off to form a hollow tube.
During secondary neurulation, the neural tube forms from the coalescence of mesenchyme cells.
13
Q
What is the order of germ layer differentiation?
A
Endoderm, then mesoderm, then ectoderm.
14
Q
Define neurulation. What is the embryo called at this stage?
A
Neurulation is the initiation of organogenesis via the neural tube. The embryo is considered a neurula.
15
Q
Along which axis does the neural tube form?
A
Along the anterior-posterior axis.
16
Q
What happens if the neural tube does not close?
A
Anencephaly, or open-brain disorder.
17
Q
How does neural tube formation signaling begin?
A
The notochord, which is mesodermally-derived, signals the ectoderm above it to become the neural tube.
18
Q
What signals does the notochord secrete to initiate primary neurulation?
A
Chordin, Noggin, Follistatin, and Shh.
19
Q
In general, how is a BMP gradient regulated?
A
Through the secretion of BMP inhibitors, especially Noggin.
20
Q
Describe how primary neurulation occurs.
A
The neural plate folds at the midline, simultaneously closing in both directions to form the neural tube.
21
Q
Describe how primary neurulation occurs, and which part of the neural plate it involves.
A
Primary neurulation occurs by proliferation of the rostral (cephalic) portion of the neural plate, followed by their invagination to form an underlying hollow tube.
22
Q
Describe how junctional neurulation occurs, and which part of the neural plate it involves.
A
Junctional neurulation at the neural plate’s midline occurs by a combination of primary and secondary neurulation.
23
Q
Describe how secondary neurulation occurs, and which part of the neural plate it involves.
A
Secondary neurulation occurs when the mesenchymal cells at the caudal (anti-cephalic) portion of the neural plate aggregate into a solid cord which then hollows out to form a tube.
24
Q
Which organisms undergo primary neurulation?
A
Only vertebrates.
25
What is secondary neurulation evolutionarily associated with?
The evolution of limbs and tails.
26
When does primary neurulation occur in the chick embryo?
At about 24 hours of development.
27
What is unique about primary neurulation in the chick embryo?
The rostral end will have undergone neurulation while the caudal end is still undergoing gastrulation.
28
At what end does the neural tube first close?
The rostral end.
29
Explain primary neurulation in a chick embryo, stating all the stages.
During elongation, the neural plate proliferates in the same plane, extending it.
During folding, the medial hinge point (MHP) cells anchor to the notochord and change their shape while epidermal cells move towards the dorsal midline.
During elevation, the MHP cells are apically constricted, closing the plate and forming a neural groove.
During convergence, the dorsolateral hinge point (DLHP) cells are apically constricted, forming the neural folds.
During closure, the neural folds are brought into contact with each other.
At this stage, the neural crest cells disperse, leaving the neural tube separate from the epidermis.
30
Name the stages of primary neurulation.
Elongation, Folding, Elevation, Convergence, and Closure.
31
Name the hinge points in primary neurulation and their significance.
The medial hinge point cells form the neural groove, and the dorsolateral hinge point cells form the neural folds.
32
Explain the mechanism of hinge point cell constriction.
The secretion of Noggin at the basal end of the hinge point cells deactivates BMP, expanding the basal components and loosening the junctional complexes. At the apical end, no Noggin is expressed, and this increased BMP leads to an apically stabilized Par complex which pulls cytoskeletal components together, forming this hinged structure.
33
What happens if BMP is over-expressed and under-expressed at the basal end of the hinge point cells?
If over-expressed, the hinge point fails to form due to constriction on both the apical and basal ends.
If under-expressed, the hinge point is exaggerated, leading to abnormal neural tube formation.
34
What happens if BMP is over-expressed and under-expressed at the apical end of the hinge point cells?
If over-expressed, the hinge point is exaggerated, leading to abnormal neural tube formation.
If under-expressed, the hinge point fails to form due to expansion on both the apical and basal ends.
35
What happens when BMP and Par proteins interact?
The cell is polarized at the Par end, forming a more rigid cell morphology due to the aggregation of cytoskeletal components.
36
After the neural tube forms, how is it internalized?
When the neural folds are brought together, the surface ectoderm cells of both ends are put in contact, facilitating their connection. This is made possible since the neural plate cells express N-cadherin whereas the epidermal cells express E-cadherin.
37
How many closure initiation sites are there in mice? Where are they positioned and where do they extend?
Closure 1 occurs between the posterior neuropore and the hindbrain neuropore. Bidirectional.
Closure 2 occurs between the hindbrain neuropore and the anterior neuropore. Bidirectional.
Closure 3 occurs at the anterior-most neuropore. Posterior closure.
38
What happens if Closure 1 in mice fails to complete?
Craniorachischisis (anterior failure) or spina bifida (posterior failure).
39
What happens if Closure 2 in mice fails to complete?
Anencephaly (any failure).
40
What happens if Closure 3 in mice fails to complete?
Anencephaly, but to a lesser extent than Closure 2.
41
How many closure initiation sites are there in humans? Where are they positioned and where do they extend?
In order of A to P:
Closure 3 occurs at the anterior-most neuropore. Posterior closure.
Closure 2 occurs at the mesencephalic–rhombencephalic boundary. Bidirectional.
Closure 4 occurs at the mesencephalic-cervical junction. Anterior closure.
Closure 1 occurs at the future cervical–thoracic junction. Bidirectional.
Closure 5 occurs at the posterior-most neuropore. Anterior closure.
42
What happens if Closure 1 in humans fails to complete?
Craniorachischisis.
43
What happens if Closures 2&3 in humans fail to complete?
Anencephaly.
44
What happens if Closure 5 in humans fails to complete?
Spina bifida.
45
How do somites indicate the embryonic age?
The number of somites indicates the stage in development as they always form at a specific embryonic "age."
46
Define anencephaly, and what closure failures cause it in mice and humans.
Anencephaly is the failure to close the neural tube at sites 2&3 in mice and sites 2&3 in humans. The forebrain remains in contact with the amniotic fluid and subsequently degenerates.
47
Define spina bifida, and what closure failures cause it in mice and humans.
Spina bifida is the failure to close the neural tube at the posterior-most neuropore in mice and site 5 in humans. The spinal cord sticks out through an opening in the spine, leading to permanent nerve damage. Babies with spina bifida often have a fluid-filled sac which may contain part of the spinal cord and its meninges. It may be genetically or environmentally caused, and leads to nerve weakness or paralysis, bowel or bladder control issues, and learning problems.
48
Define craniorachischisis, and what closure failures cause it in mice and humans.
Craniorachischisis is the failure to close the neural tube at site 1 in mice and site 1 in humans. The brain and spinal cord remain open, and fetuses with this disorder often miscarry or die shortly after birth. Causes are multifactorial.
49
What mutation in mice is associated with exencephaly and open spina bifida in mice?
The curly tail mutation, a hypo-morphic mutation in the grainhead-like3 gene.
50
What is exencephaly?
During exencephaly, the brain is located outside the skull. Usually an early stage of anencephaly whereby the neural tissue gradually degenerates as it is in contact with amniotic fluid. Exencephaly may be treated, but anencephaly may not.
51
How are curly-tailed mice different than mice with normal tails?
They may have spina bifida.
52
What environmental factors may affect human neural tube closure? How?
Drugs, maternal factors, dietary factors such as folate and cholesterol, diabetes, and obesity. They may cause changes in the epigenetic landscape of an embryo, affecting DNA CpG methylation patterns and chromatin modification, thus modifying the expression of neural tube defect genes.
53
What are the two components of folic acid?
Pteroyl, or pteroic acid, and glutamic acid.
54
Describe the folic acid pathway.
Folic acid is turned into dihydrofolate (DHF) by the dihydrofolate reductase (DHFR) enzyme. Then, DHF is converted to intermediates which are then converted to the biologically-active 5-methyltetrahydrofolate (5-MTHF) by the methyltetrahydrofolate reductase (MTHFR) enzyme. 5-MTHF is then converted to methionine by methionine synthase, which later leads to the formation of S-adenosyl methionine (SAM).
55
Which enzyme requires vitamin B12 as a cofactor?
Methionine synthase, which converts homocysteine to methionine by methyl transfer from 5-MTHF.
56
What is vitamin B9 also known as?
Folate.
57
What is vitamin B12 also known as?
Cobalamin.
58
What is the toxic product of folic acid metabolism? What happens to it?
Homocysteine, recycled into methionine.
59
What is a myelomeningocele?
The incompletion of spinal cord formation, and the most severe form of spina bifida. The baby has a protruding sac from the lower back containing nerves and meninges.
60
What is spina bifida occulta?
The least serious form of spina bifida.
61
How does the neural tube closure of fish differ from that of humans?
In fish, neural tube closes unidirectionally.
62
What are the three primary brain vesicles in humans?
The forebrain (prosencephalon), the midbrain (mesencephalon), and the hindbrain (rhombencephalon).
63
How is the anterior-posterior patterning of the hindbrain and spinal cord controlled in humans?
The Hox gene complexes.
64
What parts of the nervous system do the Hox genes affect?
Mainly the spinal cord and hindbrain, but not the midbrain and forebrain.
65
What does each primary brain vesicle develop into?
The secondary vesicles.
Forebrain into telencephalon and diencephalon.
Midbrain into mesencephalon.
Hindbrain into metencephalon and myelencephalon.
66
What are neuroepithelial progenitor cells?
Cells of the early neural tube. They can be divided into different domains based on unique transcription factor expression.
67
What are the two signaling centers of a newly-formed neural tube?
The roof plate, which is exposed to BMP4, BMP7, dorsalin, and activin from the epidermis, and the floor plate, which is exposed to Shh from the notochord.
68
How is the CNS patterned?
Based on the cell's proximity to the epidermis (roof plate) and notochord (floor plate), experiencing a unique combination of BMP4, BMP7, and Shh.
69
As [BMP] decreases and [Shh] increases, what factors are expressed in the CNS during patterning? What cell fates would they lead to?
Highest to lowest BMP and lowest to higher Shh: Pax7, Pax3, Pax6, Nkx6.1.
Pax7 is expressed in the dorsal-most neurons in the brain, Pax3 is in those directly ventral to Pax7 in the brain, then Pax6 in the intermediate interneuron cells, and Nkx6.1 is immediately dorsal to the floor plate in the motor neurons.
70
During CNS patterning, which cells are closest to the notochord?
The floor plate cells.
71
What happens if a second notochord is added in proximity to the neural tube during CNS patterning?
A second floor plate would be formed. A similar effect is observed when other Shh-secreting cells are added.
72
What are some features that distinguish the human brain from that of other species?
Cerebral cortical folding, human-specific genes and developmental alleles, high levels of transcription, and brain maturation into adulthood.
73
When does the human brain stop gaining mass?
Right after puberty.
74
How are brain structures correlated with intelligence?
An increase in number and intricacy of gyri and sulci (hills and valleys) is correlated with intelligence.
75
What do you call a brain with a lot of folds? What about one without folds?
Gyrencephalic: Folded.
Lissencephalic: Unfolded.
76
When does neurogenesis occur in humans compared to other primates?
Humans' brains develop until puberty, and the generation of neurons in a newborn occurs at the same rate as that of a fetus. Other primates attenuate neurogenesis at birth.
77
Do humans have a smaller or larger brain:body ratio compared to apes? By approximately how much?
Larger by 3.5x.
78
What happens when the brain stops growing?
Some neuronal synapses begin decaying. This occurs around the time when language acquisition becomes difficult. Myelination continues through adulthood, with gray matter decreasing and white matter increasing over the cortical surface, especially at the frontal lobe which is correlated with reasoning.
79
What is a primary difference observed between male and female brains?
Males have an increase in synapses associated with motor function whereas women have an increase in synapses associated with reasoning.
80
What is the neural crest?
A population of cells derived from the ectoderm that are characterized by moderate BMP levels.
81
How is the neural crest formed?
Cells from the dorsal neural tube undergo an EMT then migrate along the A/P axis to produce certain tissues.
82
What are the neural crest derivatives?
The PNS, the CNS-synapsed ganglia, melanocytes, facial cartilage, dentine of teeth, adrenal medullae, and the skeletal and connective tissue of the head.
83
How can the neural crest be divided?
Cranial neural crest cells.
Cardiac neural crest cells (Somites 1 to 3).
Trunk neural crest cells (Somite 6 to the tail).
Vagal & sacral neural crest cells (Somite 1 to 7 & 28).
84
Along what axes do neural crest cells travel?
The dorsoventral axis, but not the anterior-posterior axis.
85
What are the cranial neural crest cells and their derivatives?
Rostral-most fates.
The craniofacial mesenchyme differentiates into cartilage, bone, cranial neurons, glia, and melanocytes.
Through the pharyngeal arches, some cells form the bones of the middle ear and jaw, including the hyoid.
86
What are the cardiac neural crest cells and their derivatives?
Subregion of the cranial neural crest, extending from the otic region to the third somites.
Differentiate into the entire muscular and connective tissue wall of the large arteries and the septum that separates pulmonary circulation from the aorta.
87
What is the precursor of the aorta and pulmonary artery? How does it differentiate?
The truncus arteriosus. Cardiac neural crest cells deposit travel to the vessel's outflow region to induce a spiral septum formation. At the end, the aorta is positioned posterior-right and the pulmonary artery anterior-left.
88
What is a cardiac neural crest cell marker?
Pax3.
89
What are the trunk neural crest cells and their derivatives?
Neural crest cells extending from somite 6 to the tail.
Cells that migrate ventro-laterally through the anterior half of each sclerotome form the dorsal root ganglia in the sclerotome and the sympathetic ganglia, adrenal medulla, and aortic nerve clusters at the ventral-most region.
Cells that migrate dorsolaterally form melanocyte precursors.
90
How are the trunk neural crest cells organized into their respective fates?
The presence of ephrin repels these neural crest cells, ensuring that they only occupy the anterior portion of each somite. This allows melanocytes to be properly positioned and ensures that the neural ganglia do not cross-connect.
91
What are the vagal and sacral neural crest cells and their derivatives?
Neural crest cells extending from somite 1 to 7 (vagal) and somite 28 (sacral).
The vagal neural crest cells are localized opposite to their respective ventral somites, at the dorsal side of the neural tube.
Differentiate into the parasympathetic ganglia of the gut.
92
What happens when vagal and sacral neural crest cells fail to migrate into the colon?
The absence of enteric ganglia and no peristaltic movement in the bowels.
93
T/F: Pre-migratory neural crest cells still attached to the neural tube are already specified to be neural crest cells.
True.
94
T/F: Pre-migratory neural crest cells already have a specified lineage (cranial, cardiac, ...).
False.
95
Ectodermal cells with high Wnt and BMP differentiate into:
Epidermal cells.
96
Ectodermal cells with moderate Wnt and BMP differentiate into:
Placodal cells.
97
Ectodermal cells with high Wnt but moderate BMP differentiate into:
Neural crest cells.
98
Ectodermal cells with high Wnt but no BMP (high Noggin) differentiate into:
Neural cells.
99
What do placodal cells give rise to?
Sensory and neuroendocrine cells.
100
What factors induce the neural plate border specifiers?
Wnt & BMP.
101
What factors determine the neural plate border?
Msx1.
102
What factors are neural crest specifiers?
FoxD3, Sox9/10, & Snail.
103
What factors facilitate EMT in the neural crest?
Sox9 & Sox10.
104
What features are necessary for EMT of neural crest cells?
Loss of E-cadherins-6B, cytoskeletal rearrangement, actin polymerization, increase of integrins and fibronectin in the ECM, decreased N-cadherin expression, and delamination.
105
Are neural crest cells void of cadherins?
Mostly yes, except for some N-cadherins that allow them to travel as a unit.
106
How do neural crest cells travel as a unit?
Some minimal expression of N-cadherins, and the secretion of a chemoattractant Complement 3a (C3a).
107
Describe the signals involved in neural crest delamination.
The surface ectoderm first induces high Snail2 release, and the notochord releases Sox2. These two factors inhibit each other, forming a gradient. Snail2 inhibits E-cadherins-6b and N-cadherins to a lesser extent, especially at the dorsal site where neural crest cells are supposed to delaminate. Ventrally, the high Sox2 from the notochord inhibits Snail2, preserving these cadherins and maintaining the epithelial character of neural tube cells.
108
How do neural crest cells travel?
Upon delamination, a RhoA/Rac1 gradient is established by cellular polarization. At the rear, a high RhoA concentration is associated with actomyosin stress fiber retraction whereas, at the front, a high Rac1 concentration is associated with directed movement by lamellipodia and filopodia.
109
What role does the microphthalmia-associated transcription factor (MITF) play in ectodermal signaling?
It is linked to pigmentation disorders, specifically involved in the activation of genes responsible for pigment production, in the proper dorsolateral migration of neural crest cells into the skin, and in preventing apoptosis in migrating cells.
110
In animals, the random death of melanoblasts and spotted patterns is associated with which factor?
The microphthalmia-associated transcription factor (MITF).
