May22 M1-Embryonic development of vertebral column and limbs 1

Question 1

when vertebra form

Answer 1

• after nervous system forms (will associate with it)

- early in gastrulation when notochord forms

Question 2

name of the earliest event for body innervation and segmentation

Answer 2

principle of original innervation

Question 3

principle of original innervation

Answer 3

• in gastrulation, segmentation of body because newly-formed mesenchyme makes a segment pattern
• a midline segmented vertebral column + paired nerves form. is the basis for tissue innervation

Question 4

2 key things that happen in gastrulation

Answer 4

1. formation of all mesenchymal stem cells

2. initial hox gene expression

Question 5

first structure forming in gastrulation

Answer 5

notochord in midline

Question 6

what forms the notochord

Answer 6

intra-embryonic mesenchyme

Question 7

3 functions of notochord

Answer 7

1. induce overlying primitive ectoderm to form neural plate (neurectoderm of the future neural tube) (prechord also called prechordial plate also helps for this induction)
2. induce the PNS
3. induce the vertebral column later on

Question 8

portions of the neural plate (formed by primitive ectoderm after notochord induced that)

Answer 8

• forebrain, midbrain, hindbrain

- spinal cord crossing all that in the middle

Question 9

cells on the periphery of the neural plate after it forms and their function

Answer 9

NCCs

-will form the PNS later on

Question 10

how neural plate becomes neural tube (with name of process)

Answer 10

• neurulation*
• neural plate forms and forms a neural tube
• surface ectoderm folds and pinches, forming the skin. comes on both sides and closes over the neural tube

Question 11

how NCCs on periphery of neural plate behave during neurulation

Answer 11

• initially, have neural plate + NCC on their periphery + surface ectoderm around all that
• NCCs move towards the axis of folding of neural plate (as if guiding the folding)

Question 12

NCC type of cells

Answer 12

stem cells

Question 13

(imp) what NCCs do after neurulation

Answer 13

• migrate into whole embryo

- will induce the PNS most importantly like segmental dorsal root ganglia (among other tissues)

Question 14

one consequence of neural tube formation

Answer 14

induces the formation of mesenchyme

Question 15

during gastrulation, what cells (and in what region) induce the neural plate

Answer 15

• have pritimive streak and node (node = most mesenchyme forming there)
• mesenchyme goes up in the middle axis to form neural plate by inducing notochord

Question 16

during gastrulation, how is segmental pattern established

Answer 16

some strike and node mesenchymal cells migrate laterally to form segmental pattern

Question 17

first transcription initiation events in the embryo

Answer 17

hox genes (are segmental genes so allows segmental pattern) expressed by mesenchymal cells of strike and node that went laterally in gastrulation

Question 18

how hox genes spread

Answer 18

• hox gene expressing region becomes larger, in the cranio-caudal direction
• initially loose mesenchyme and then aggregates (forming somites)

Question 19

from near the neural plate (with underlying notochord) to outside of the trilaminar embryo, names of layers of (mesoderm) segmentation

Answer 19

1. paraxial mesoderm (closest to axis of neural plate) (somites)
2. intermediate mesoderm
3. lateral plate mesoderm

Question 20

key cellular event for gastrulation and NCC formation and key cellular event for mesenchyme aggregation

Answer 20

• epithelial mesenchymal transition (EMT): for gastrulation and NCC formation
• MET for mesenchymal aggregation (after it becomes epithelial in nature)

Question 21

name of the structures formed by mesenchyme aggregation and what they express

Answer 21

somites (paraxial mesoderm)

• express retinoic acid which is an important regulator of the hox gene
• express hox gene

Question 22

consequence of retinoic acid expression by somites

Answer 22

• induction of the adjacent spinal cord

- FUNCTIONAL (but not structural) separation of this spinal cord (in segments)

Question 23

when do neurulation and somite development happen with respect to each other

Answer 23

both together at the same time at 22-25 days

Question 24

somites are what region of mesoderm on the side of the neural plate (segments formed by hox genes)

Answer 24

paraxial mesoderm

Question 25

last region to close (end of neural tube formation) in neurulation

Answer 25

caudal region

Question 26

important concept that links spinal cord and somites (mesenchyme aggregation (MET) and retinoic acid, etc.)

Answer 26

molecular linking between the spinal cord and the somites (the somites will lead to the spinal cord via retinoic acid)

Question 27

after neurulation, what do NCCs form along the neural tube (think of what they become)

Answer 27

- aggregate to form the dorsal root ganglia that are segmented (associate with a somite and a region of the spinal cord) - will also form the meninges around the spinal cord and brain

Question 28

what's a dorsal root ganglion in the spinal cord

Answer 28

- cell bodies with dendrites projecting to tissues (and periphery, rest of the body) and axons projecting to the spine - brings sensory info to the spine

Question 29

segmentation of the spine with somites and dorsal root ganglia: what is the clinical relevance

Answer 29

explains the dermatomes and the myotomes patterns

Question 30

what forms the meninges (dura mater, arachnoid, pia mater)

Answer 30

NCCs

Question 31

what forms the SS chain and the PNS

Answer 31

NCCs

Question 32

after you have the neural tube completely formed with dorsal root ganglia, meninges, etc. what do somites do

Answer 32

on each side of the neural tube (of every neural tube level), somites form a cavity with a dermo-myotome on its outside and a sclerotome on its inside

Question 33

how do somites form cavities on each side of the neural tube

Answer 33

because mesenchymal stem cells in somites become differentiated, commit to form diff cell types (dermo-myotome cells, sclerotome cells)

Question 34

dermo-myotome will form what

Answer 34

- the dermis under the epithelium | - the myotome will form the skeletal muscle (stem cells will differentiate)

Question 35

what will the sclerotome form

Answer 35

CT, specialized CT, cartilage and bone

Question 36

as the neurulation is completed, what does the lateral plate mesoderm do

Answer 36

it forms a cavity (the intra-embryonic coelum) separating the somatopleure (body wall) from the splanchnopleure (gut wall)

Question 37

what will the sclerotome do relating to the neural tube and what induces that

Answer 37

- differentiates and migrates around the neural tube to form the vertebra - NCCs induce that

Question 38

gene that the notochord and floor plate of the neural tube continue to form (and have been forming since before neurulation)

Answer 38

sonic hedgehog. (SHH). It diffuses through neural tube, towards the sclerotome and this expression of SHH keeps diffusing laterally

Question 39

other gene that diffuses towards the sclerotomes

Answer 39

bone morphogenetic protein 4 (BMP4) | -comes from roof plate of the embryo

Question 40

what is the effect of SHH FROM THE NOTOCHORD***on sclerotomes

Answer 40

- induces EMT in ventro-medial somitic cells (initially mesenchymal SCs did MET to aggregate and form somites) - induces these new mesenchymal stem cells to make Pax-1 - Pax-1 is important for cartilage and bone production by the sclerotome

Question 41

function of Pax-1 expressed by sclerotomal cells

Answer 41

- is a TF | - important for cartilage and bone production

Question 42

effect of BMP4 on the sclerotomes

Answer 42

induces sclerotome mesenchymal stem cells expressing Pax-1 to migrate around the neural tube

Question 43

pattern of migration of sclerotomes around the neural tube

Answer 43

go towards the roof to form the lamina and go outwards to form the transverse processes of the vertebrae

Question 44

what determines the shape of the vertebra

Answer 44

diff types of hox genes being expressed at this stage still (where vertebrae being formed by sclerotome wrapping around) and will determine this segmentation: cervical, thoracic and lumbar vertebrae

Question 45

structures formed by sclerotome migrating around notochord and neural tube on both sides

Answer 45

- lamina (fuses to form spine of the vertebra) - centrum (body of the vertebra) and IV disc - transverse process - pedicle

Question 46

what induces the lamina to make it fuse and form the spine of the vertebra

Answer 46

the roof plate

Question 47

2 sources of formation of the vertebra and clinical relevance

Answer 47

ventral and dorsal aspect | -bad closure of neural tube = dorsal portion poorly stimulated and not formed properly

Question 48

what determines the cartilage model of vertebrae and what gives each vertebra its unique structure (needed for its spinal level)

Answer 48

cranial-caudal expression of a unique combination of hox genes. important until chondrification (basic form of vertebra being established) begins

Question 49

what happens if the neural tube/the lamina don't close right

Answer 49

get spina bifida (a bifid vertebral spine (spinous process))

Question 50

possible defect in the cervical spine if there is an abnormal hox code expression and significance clinically

Answer 50

``` cervical rib (formed by transverse process) -can compress the brachial plexus and the nerves going to rib 1 ```

Question 51

what can be the cause of an abnormal hox code expression leading to a cervical rib

Answer 51

retinoic acid abnormalities during the termination of the hox cord (end of hox cord pattern being established)

Question 52

what forms the centrum and IV disc at one spinal level

Answer 52

2 sclerotomes (one from each side)

Question 53

what does the notochord do as the vertebra is being formed by the 2 sclerotomes

Answer 53

- regresses - helps for IV disc formation - will always remain as the nucleus pulposus in the IV disc

Question 54

how many cervical vertebra and how many cervical nerves

Answer 54

7 C vertebra 8 C nerves shift between vertebra level and nerves level

Question 55

position of nerves relative to vertebrae in cervical and thoracic spinal levels

Answer 55

``` C: nerve above corresponding vertebra T: nerve is below corresponding vertebra C7 nerve is above C7 vertebra C8 nerve is below C7 vertebra T1 nerve is below T1 vertebra ```

Question 56

shape of the vertebral column in the embryo

Answer 56

C shape (kyphosis all the way) inwards

Question 57

step after C shape column in the embryo

Answer 57

sacrum starts forming

Question 58

step after sacrum starts forming in the C shape column in embryo

Answer 58

neck starts forming

Question 59

step after neck and sacrum formed in the C shape column

Answer 59

get normal spine with C lordosis, T kyphosis, L lordosis, S kyphosis

Question 60

(important) what happens to the spine with age

Answer 60

IV discs contribute to the length of the whole vertebral column. because IV discs regress with age, the vertebral column becomes shorter and and its curvature changes