Development of the neural tube Flashcards
what is the first identifiable feature in the formation of the neural tube?
the notochord
what is the process of gastrulation?
cells near the primitive streak of the blast invaginate into the embryonic disc
produces the 3 germ layers
what is the notochord?
signalling centre, transient structure, plays a major role in embryo folding and controls the direction of embryo folding
what happens at the beginning of week 3 of development?
the ectodermal germ layer broadens at the cephalic area (where the future head will be)
notochord arises from this area
which region does the notochord arise from?
the cephalic area
what do the cells of the notochord contribute to after fetal life?
cells of the nucleus pulposus of the IVD after fetal life
what do signals from the notochord do?
induce development in the neural plate and the overlying ectoderm
signals involved are the proteins noggin and chrodin
what are the 2 important protein signals involved from the notochord?
proteins noggin and chordin
what kind of signals are proteins noggin and chordin?
negative regulators of development
presense activates inhibition of other molecules
what does the absence of BMP4 mean?
the patterning of the neural tube and somites can occur
what would happen if BMP was present?
no neural tube would form
what do the cells of the neural plate make up?
neural ectoderm
what is the depression in the middle of the 2 neural folds called?
neural groove
what happens to the lateral edges of the neural plate and it lengthens?
they start to elevate to make two neural folds with a depression in the middle
when is the neural tube formed?
when the folds eventually meet together and fuse
what happens after the neural tube is formed?
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
what does the neural tube go on to form?
the brain and the spinal cord
what mechanism controls the bending of the neural plate?
-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)
what are the mechanical controls of the bending of the neural plate?
cells become a bit more wedge shape which pushes the tube to form
what process is the most important in the bending of the neural plate?
formation of hinge points
when in development does the lateral edges of the neural plate become elevated?
day 19
where are the hinge points?
the median hinge point - at the region of the neural groove
dorsolateral hinge point- dorsolateral side of the embryo help close the tube
what are neural crest cells?
highly migratory cells that form at the time of new relation
move all through the embryo body and give rise to varied structures
what kind of structures do the neural tube cells give rise to?
craniofacial structures
melanocytes
dorsal root ganglia
teeth
where does fusion start?
cerviacle region of the embryo
proceeds in a cephalic and caudal direction simultaneously
what are the anterior and posterior neuropores?
the ends of the neural tube which have not yet fused
when does closure of the neural pores occur?
week 4
anterior - closed by day 25
posterior - day 27
what causes the ectoderm to thicken up and become the neural ectoderm?
the notochord and mesoderm
what causes congenital issues to arise?
10%- environmental
10-15% chromosomal
20-25% multifactorial genetic predisposition with environment correct for expression
50-60% unknown
generally what percentage of infants show forms of defects?
3%
what are some examples of minor issues which happen in newborns?
pigmented spots
small ears
short papebral fissures
what is the chance of an infant with a minor defect having a major health issue?
1 defect - 3%
2 defects -10%
3 or more -20%
what are teratogens?
an agent or substance that can disturb the development of an embryo or foetus
the timing of exposure is essential for the effect
what are the stages of embryology?
pre germ layer- week 1-2
embryonic period -week 3-8
fetal period - week 9-38
what is the effects of teratogens week 1-2?
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
what effects can teratogens have on the embryo in weeks 9-38?
-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
what effects can teratogens have on the embryo in weeks 3-8?
-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
what Factors can increase the risk of a baby developing a neural tube defect during pregnancy?
-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
what is folate?
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.
what is folate a term for?
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.
what is the difference between food folate and folic acid?
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.
what kind of drugs can interfere with folate metabolism?
epilepsy drugs as they can inhibit folate —-Valproate
what is the signalling pathway that comes close to being the “master controller”?
sonic hedgehog (SHH)
what is sonic hedgehog (SHH)?
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
which area of the neural tube is the responder to SHH?
ventral area - tube differentiates in this region and makes the floor plate of the neural tube
what happens once the floor plate has differentiated?
creates its own SHH and signals other cells in the area to differentiate into motor neurons at each side of the tube
what does SHH causing epithelia-mesenchymal transformation allow?
-allows cells to migrate
-move toward the signal source
-form the vertebral column around the notochord
what effect does SHH have on the dermomyotome?
induces competence to respond to signals from the surface ectoderm
which hinge points are missing in the upper spine?
dorsolateral hinge points - medial hinge point is enough to close the tube
what does BMP 2 cause?
absence of the hinge points
what does noggin do?
inhibits BMP’s
what happens in the lower spine when closing?
SHH is reduces and noggin is un-inhibited and it antagonises BMP2 which allows DLHP’s to form
what effect foes SHH have on noggin?
inhibition
what are the levels of SHH like from the upper spine to lower?
a gradient
higher at upper spine
lower in lower spine
what defects can increased SHH cause?
neural tube defects in the Lower spine as it suppresses formation of DLHPs altering closure
What is a zygote?
Fertilised oocyte
What is cleavage?
Diving of zygote to form a ball of blastomeres
What is the zona pellucida?
Glycoprotein coat helps prevent polyspermy and ectopic implantation?
What is the trophoblast?
Outer cells of blastocyst which will form placental structures
If a a baby is born with fusion of the digits what gene is a mutation likely happened in?
HOXD13
What is a derivative of the neural crest cells?
Dorsal root ganglia
At which point in gestation would a virus most likely cause issues with the senses?
Weeks 4-8
Which type of mesoderm surrounds the amniotic cavity?
Parietal/somatic
From which structure does the nervous system originate from?
Neural tube
which structures arise from the endoderm?
pancreas, liver, thymus, thyroid gland
which structures arise from the mesoderm?
notochord, muscular system, skeletal system, reproductive system
