Development of the neural tube Flashcards

1
Q

what is the first identifiable feature in the formation of the neural tube?

A

the notochord

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1
Q

what is the process of gastrulation?

A

cells near the primitive streak of the blast invaginate into the embryonic disc
produces the 3 germ layers

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2
Q

what is the notochord?

A

signalling centre, transient structure, plays a major role in embryo folding and controls the direction of embryo folding

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3
Q

what happens at the beginning of week 3 of development?

A

the ectodermal germ layer broadens at the cephalic area (where the future head will be)
notochord arises from this area

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4
Q

which region does the notochord arise from?

A

the cephalic area

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5
Q

what do the cells of the notochord contribute to after fetal life?

A

cells of the nucleus pulposus of the IVD after fetal life

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6
Q

what do signals from the notochord do?

A

induce development in the neural plate and the overlying ectoderm
signals involved are the proteins noggin and chrodin

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7
Q

what are the 2 important protein signals involved from the notochord?

A

proteins noggin and chordin

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8
Q

what kind of signals are proteins noggin and chordin?

A

negative regulators of development
presense activates inhibition of other molecules

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9
Q

what does the absence of BMP4 mean?

A

the patterning of the neural tube and somites can occur

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10
Q

what would happen if BMP was present?

A

no neural tube would form

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11
Q

what do the cells of the neural plate make up?

A

neural ectoderm

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12
Q

what is the depression in the middle of the 2 neural folds called?

A

neural groove

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12
Q

what happens to the lateral edges of the neural plate and it lengthens?

A

they start to elevate to make two neural folds with a depression in the middle

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13
Q

when is the neural tube formed?

A

when the folds eventually meet together and fuse

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14
Q

what happens after the neural tube is formed?

A

the hole of the tube sinks down into the body of the embryo and the surface ectoderm will appear over the top of the newly formed tube

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15
Q

what does the neural tube go on to form?

A

the brain and the spinal cord

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15
Q

what mechanism controls the bending of the neural plate?

A

-cell wedging (microtubules and microfilaments changing cell shape, cell cycle)
-hinge points (median hinge point and dorsolateral hinge point)
-extrinsic forces (pushing the surface ectoderm, adhesion point with the notochord)

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16
Q

what are the mechanical controls of the bending of the neural plate?

A

cells become a bit more wedge shape which pushes the tube to form

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17
Q

what process is the most important in the bending of the neural plate?

A

formation of hinge points

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18
Q

when in development does the lateral edges of the neural plate become elevated?

A

day 19

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18
Q

where are the hinge points?

A

the median hinge point - at the region of the neural groove
dorsolateral hinge point- dorsolateral side of the embryo help close the tube

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19
Q

what are neural crest cells?

A

highly migratory cells that form at the time of new relation
move all through the embryo body and give rise to varied structures

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20
Q

what kind of structures do the neural tube cells give rise to?

A

craniofacial structures
melanocytes
dorsal root ganglia
teeth

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21
Q

where does fusion start?

A

cerviacle region of the embryo
proceeds in a cephalic and caudal direction simultaneously

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22
Q

what are the anterior and posterior neuropores?

A

the ends of the neural tube which have not yet fused

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23
Q

when does closure of the neural pores occur?

A

week 4
anterior - closed by day 25
posterior - day 27

24
Q

what causes the ectoderm to thicken up and become the neural ectoderm?

A

the notochord and mesoderm

25
Q

what causes congenital issues to arise?

A

10%- environmental
10-15% chromosomal
20-25% multifactorial genetic predisposition with environment correct for expression
50-60% unknown

25
Q

generally what percentage of infants show forms of defects?

A

3%

26
Q

what are some examples of minor issues which happen in newborns?

A

pigmented spots
small ears
short papebral fissures

27
Q

what is the chance of an infant with a minor defect having a major health issue?

A

1 defect - 3%
2 defects -10%
3 or more -20%

28
Q

what are teratogens?

A

an agent or substance that can disturb the development of an embryo or foetus
the timing of exposure is essential for the effect

29
Q

what are the stages of embryology?

A

pre germ layer- week 1-2
embryonic period -week 3-8
fetal period - week 9-38

30
Q

what is the effects of teratogens week 1-2?

A

either have no effect or the conceptus will be spontaneously aborted
-if one two cells are killed, the first embryo can compensate (regulative development)
-if more cells are killed the embryo is lost, often before the pregnancy is confirmed

31
Q

what effects can teratogens have on the embryo in weeks 9-38?

A

-functional deficits and minor abnormalities are produced by teratogens acting this stage
-susceptibility to teratogens is reduced
-differentiation is occurring at this stage- any organ still differentiating is still vulnerable eg urogenital and NS
-usually functional deficits that occur, generally not as severe

31
Q

what effects can teratogens have on the embryo in weeks 3-8?

A

-organ systems are being established
-most teratogens are highly effective at this stage
-each organ system has its own period of maximum sensitivity
-type of defect seen depends on which organ system is most vulnerable at a particular time that the teratogen acts

32
Q

what Factors can increase the risk of a baby developing a neural tube defect during pregnancy?

A

-Not enough folate prior to and during the first 3 months of pregnancy
-The use of certain medications (for example, drugs used to treat epilepsy)
-Environmental factors
-Ethnic background - More common in people of Celtic origin
-Genetics – e.g aberrant sonic hedgehog signalling, having one child with spina bifida increases risk of a future pregnancy being affected

33
Q

what is folate?

A

Folate acts as a co-factor for enzymes involved in DNA and RNA biosynthesis. If there is not enough folate, then this can affect DNA synthesis, and at this time of development, the embryo is undergoing huge amounts of cell proliferation to create enough cells for the embryo to undergo neuralation and organogenesis, so any effect on cell proliferation can affect many processes.

34
Q

what is folate a term for?

A

generic term for a water soluble B-vitamin that serves as an essential co-enzyme in single carbon transfers in the metabolism of nucleic and amino acids. Folic acid is the oxidised and most active form of the vitamin. It is found rarely in food (hence the need to supplement in the diet), it is the form used in vitamin preparations and food fortification.

35
Q

what is the difference between food folate and folic acid?

A

The distinction between food folate and folic acid is important because of differing bioavailability. Food folate is only about half as available as folic acid consumed on an empty stomach. The MRC study led to the introduction of mandatory folic acid to flour in around 80 countries.

36
Q

what kind of drugs can interfere with folate metabolism?

A

epilepsy drugs as they can inhibit folate —-Valproate

37
Q

what is the signalling pathway that comes close to being the “master controller”?

A

sonic hedgehog (SHH)

38
Q

what is sonic hedgehog (SHH)?

A

plays a critical role in patterning the neural tube
released by notochord and passes the developing neural tube
critical role in development of brain and spinal cord
-roles in somite patterning and limb bud development
-works at a short range (ONLY ACTS ON ADJACENT TISSUES)
-causes cells in the ventral part of the somite to form the sclerotome

39
Q

which area of the neural tube is the responder to SHH?

A

ventral area - tube differentiates in this region and makes the floor plate of the neural tube

40
Q

what happens once the floor plate has differentiated?

A

creates its own SHH and signals other cells in the area to differentiate into motor neurons at each side of the tube

41
Q

what does SHH causing epithelia-mesenchymal transformation allow?

A

-allows cells to migrate
-move toward the signal source
-form the vertebral column around the notochord

42
Q

what effect does SHH have on the dermomyotome?

A

induces competence to respond to signals from the surface ectoderm

43
Q

which hinge points are missing in the upper spine?

A

dorsolateral hinge points - medial hinge point is enough to close the tube

44
Q

what does BMP 2 cause?

A

absence of the hinge points

45
Q

what does noggin do?

A

inhibits BMP’s

46
Q

what happens in the lower spine when closing?

A

SHH is reduces and noggin is un-inhibited and it antagonises BMP2 which allows DLHP’s to form

47
Q

what effect foes SHH have on noggin?

A

inhibition

48
Q

what are the levels of SHH like from the upper spine to lower?

A

a gradient
higher at upper spine
lower in lower spine

49
Q

what defects can increased SHH cause?

A

neural tube defects in the Lower spine as it suppresses formation of DLHPs altering closure

50
Q

What is a zygote?

A

Fertilised oocyte

51
Q

What is cleavage?

A

Diving of zygote to form a ball of blastomeres

52
Q

What is the zona pellucida?

A

Glycoprotein coat helps prevent polyspermy and ectopic implantation?

53
Q

What is the trophoblast?

A

Outer cells of blastocyst which will form placental structures

54
Q

If a a baby is born with fusion of the digits what gene is a mutation likely happened in?

A

HOXD13

55
Q

What is a derivative of the neural crest cells?

A

Dorsal root ganglia

56
Q

At which point in gestation would a virus most likely cause issues with the senses?

A

Weeks 4-8

57
Q

Which type of mesoderm surrounds the amniotic cavity?

A

Parietal/somatic

58
Q

From which structure does the nervous system originate from?

A

Neural tube

59
Q

which structures arise from the endoderm?

A

pancreas, liver, thymus, thyroid gland

60
Q

which structures arise from the mesoderm?

A

notochord, muscular system, skeletal system, reproductive system