Final Exam - Somite development

Question 1

Somitogenesis

Answer 1

Concomitant (happening at the same time) with neurulation

Question 2

Neurulation

Answer 2

• neural tube closure
• Concomitant (happening at the same time) with somitogenesis
• the process in vertebrates in which the future brain and spinal cord formed from the ectodermal neural plate
• as a result, largely of localized changes in cell shape, the neutral plate develops a central groove (the neural groove) with folds rising up on either side (neural folds)
• the folds eventually meet and fuse along the midline to form a tubular structure (the neural tube) that develops into the brain and spinal cord in birds and mammals
• the neural plate gives rise to the brain and spinal cord is formed from stem zone

Question 3

Notochord

Answer 3

• organizing centre
• a transient stiff, rod-like cellular structure in vertebrate embryos that runs from head to tail and lies centrally beneath the neural tube
• it is derived from mesoderm and its cells eventually become incorporated into the vertebral column

Question 4

Somites

Answer 4

• blocks of mesoderm that segment from the mesoderm on either side of the notochord
• they give rise to trunk and limb muscles, the vertebral column and ribs and the dermis

Question 5

Somites

Answer 5

• paired segmented blocks of tissue that form on either side of the notochord
• Each somite develops in a precise temporal and spatial order
• blocks of mesoderm that segment from the mesoderm on either side of the notochord
• they give rise to trunk and limb muscles, the vertebral column and ribs and the dermis
• repeating pattern
• are paraxial (on either side of the notochord)
• Patterning of the somites provides much of the anterior-posterior organization of the vertebrate body plan
• In chick, a new somite forms every 90 minutes in a precise anterior to posterior direction

Question 6

Paraxial mesoderm

Answer 6

• mesoderm lying on either side of the dorsal midline and which gives rise to the somites
• paraxial=on either side of the notochord
• Patterning of the somites provides much of the anterior-posterior organization of the vertebrate body plan

Question 7

Node

Answer 7

in avian and mammalian embryos, the embryonic organizing center analogous to the Spemann-Mangold organizer of amphibians

• also known as Henson’s node in birds
• in plants, that part of the stem at which leaves and lateral buds form

Question 8

Stem zone

Answer 8

-in avian and mammalian embryos, an arc of self-renewing epiblast cells on either side of the primitive streak immediately posterior to the regressing node that give rise to the trunk neural tube and the medial parts of the somites

Question 9

Stem zone

Answer 9

• located in and around the node containing stem cells that divide and populate the pre-somitic mesoderm
• in avian and mammalian embryos, an arc of self-renewing epiblast cells on either side of the primitive streak immediately posterior to the regressing node that give rise to the trunk neural tube and the medial parts of the somites

Question 10

Primary body formation

Answer 10

-in avian and mammalian embryos, the formation of the head and trunk from a stem cell population originating in the node and the adjacent arc of epiblast (called the stem zone)

Question 11

Secondary body formation

Answer 11

• formation of the most posterior region of the body from the tailbud in mouse and chick embryos
• Tail is formed from a pool of stem cells called the tail bud stem cells

Question 12

Tail bud stem cells

Answer 12

• Tail is formed from a pool of stem cells called the tail bud stem cells
• Originates from primitive streak and surrounding epiblast

Question 13

Pre-somitic mesoderm

Answer 13

• the unsegmented mesoderm between the node (in chick and mouse) and the already formed somites
• it will form somites from its anterior end
• This region is produced from the stem cells surrounding the node (e.g. stem zone)
• The stem zone cells are self-renewing
• Daughters contribute to the pre-somitic mesoderm which is a region located between the last somite and the regressing node
• During node regression, the pre-somitic mesoderm region remains fairly constant in length
• Changes in cell shape and intercellular connections give rise to the blocks of somite tissue as they form from this pre-somitic mesoderm

Question 14

Fgf and Wnt signalling

Answer 14

• Fgf and Wnt are signalling molecules
• expressed in node area (adjacent arc epiblast) of the mouse
• Maintain a pool of undifferentiated and proliferating (2 properties of stem cells) stem cells in the stem zone
• maintains the length of the pre-somitic mesoderm
• The highest levels of Fgf / Wnt are in the posterior with highest levels in the node
• patterns the anterior-posterior axis
• Fgf 8 mRNA is produced by the node and becomes degraded as cells move away from the node
• A Fgf 8 protein gradient is created without diffusion from a point source
• Wnt-3a, FGF Receptor 1
• Mutations in genes in the mouse result in truncation of the body axis
• A defect in maintaining the pre-somitic mesoderm
• A key transcriptional target of these pathways is expression of Brachyury
• In mouse, mutations in brachyury also cause axis truncation, probably due to the inability to regulate pre-somitic mesoderm

Question 15

Fgf8 mRNA

Answer 15

• is produced by the node and becomes degraded as cells move away from the node
• A Fgf 8 protein gradient is created without diffusion from a point source
• part of Fgf/Wnt signalling

Question 16

Wnt-3a

Answer 16

• Mutations in genes in the mouse result in truncation of the body axis
• A defect in maintaining the pre-somitic mesoderm
• part of Fgf/Wnt signalling

Question 17

FGF Receptor 1 (FGFR1)

Answer 17

• Mutations in genes in the mouse result in truncation of the body axis
• A defect in maintaining the pre-somitic mesoderm
• part of Fgf/Wnt signalling

Question 18

Brachyury

Answer 18

• a transcription factor
• important in somite development
• highly conserved
• driving specification from induction and patterning
• A key transcriptional target of the Wnt and Fgf signalling pathways is expression of Brachyury
• In mouse, mutations in brachyury also cause axis truncation
• Probably due to the inability to regulate pre-somitic mesoderm

Question 19

autonomous

Answer 19

• somite development is autonomous and follows a pattern determined earlier in development
• describes any developmental process that can continue without a requirement for extracellular signals to be continuously present
• Experiment: Take pre-somatic mesoderm, flip it around, now inverted. Instead of taking on fate of its new position (more anterior), cells still become somites, in its normal place. Therefore, somite development is autonomous
• Temporal sequence of somite formation from the pre-somitic mesoderm is autonomous. Demonstrated through chick manipulation of the pre-somitic zone. Positional identity of pre-somitic mesoderm is already pre-determined. This suggests that the A-P axis is laid down earlier in development. Probably occurring during gastrulation (e.g. primitive streak formation and elongation).

Question 20

opposing gradients of FGF and Retinoic Acid (RA)

Answer 20

• are expressed in opposing gradients
• retinoic acid antagonizes the Fgf/Wnt signalling pathways
• retinoic acid is expressed by the somites
• pattern pre-somitic mesoderm
• Retinoic acid expressed by the somites and diffuses towards the posterior
• This forms a retinoic acid gradient
• Opposing the Fgf 8 gradient is the retinoic acid gradient
• It antagonizes Fgf 8
• Functions to keep the pre-somitic mesoderm a consistent length (e.g. between the node and the last formed somite)
• Most embryos treated with excess retinoic acid have axis truncations
• The two gradients control the pre-somatic mesoderm and somite formation in a wavefront model

Question 21

wavefront

Answer 21

• for somite formation
• the node migrates towards the posterior
• regulated by threshold of Fgf/Wnt signalling
• The position of the wavefront of somite formation is specified by a drop below a threshold level of Fgf/Wnt signalling
• when the threshold level of Fgf-8 and Wnt-3 signalling drops below the threshold, somite formation can occur
• Fgf-8 gradient moves with the node as it regresses that allows for the pre-somitic mesoderm to remain a constant length
• As cells pass the determination wavefront, they receive a second signal from an oscillating clock to form a somite at a precise time interval (e.g. 90 minutes)

Question 22

Oscillating clock

Answer 22

• the clock is established by waves of c-hairy-1 expression
• allows for the precise timing of each somite
• A new somite forms every 90 minutes in the chick
• These blocks of tissue are determined by an internal clock
• This is represented by periodic cycles of gene expression
• c-hairy-1 is an example where its expression sweeps from the posterior to the anterior pre-somitic mesoderm with a period of 90 minutes
• After each wave, c-hairy-1 becomes restricted to the posterior region of each newly formed somite
• Each cycle, a given cell in the pre-somitic mesoderm experiences distinct phases when c-hairy-1 is or is not expressed
• More anterior somites have experienced fewer c-hairy waves/oscillations
• The control of c-hairy-1 expression is not well understood
• Notch-Delta signalling is necessary and is interacting with the Fgf-8/Wnt-3 gradient
• Over active or under active Notch signalling, there is a loss or irregularity of somite formation
• Fgf-8 gradient (high in node) interacts with the oscillating clock
• Timing and position of somite formation

Question 23

c-hairy-1

Answer 23

• involved in somite formation
• part of oscillating clock
• c-hairy-1 is an example of a gene where its expression sweeps from the posterior to the anterior pre-somitic mesoderm with a period of 90 minutes = oscillating clock
• After each wave, c-hairy-1 becomes restricted to the posterior region of each newly formed somite
• Each cycle, a given cell in the pre-somitic mesoderm experiences distinct phases when c-hairy-1 is or is not expressed
• More anterior somites have experienced fewer c-hairy waves/oscillations
• The control of c-hairy-1 expression is not well understood

Question 24

Delta-Notch signalling

Answer 24

• Notch-Delta signalling is necessary in the oscillating clock of somite formation
• Over active or under active Notch signalling, there is a loss or irregularity of somite formation
• important for timing and position of somite formation

Question 25

vertebrae anatomical characteristics

Answer 25

- The anterior-posterior identity of somites is best visualized through vertebrae structures - Each vertebrae has specific anatomical characteristics

Question 26

Hox genes

Answer 26

- somite identity is specified by Hox gene expression - Hox genes are a widely conserved cluster that is direct anterior-posterior identity of the mesoderm - Homeodomain containing transcription factors that bind to homeobox DNA sequences (e.g. enhancers) - Flies have a single Hox cluster (Antennapedia and Bithorax) - Most vertebrates have four of these clusters (Hox a, Hox b, Hox c and Hox d) - Within each cluster, some genes of the Antennapedia and Bithorax clusters have been deleted or duplicated - These genes are expressed in temporal (time) and spatial order that reflects their position within the complex=co-linearity (seen in drosophila, Hox genes are co-linear and have posterior dominance) - Mesodermal cells have different positional values based on Hox gene expression - The Hox Genes pattern the mesoderm and some ectodermal tissues - The Hox genes start to be expressed during early gastrulation - The most anterior genes (e.g. Hox-a1 and Hox-b1) are expressed in the most anterior tissue - More posterior genes are expressed as gastrulation proceeds - The outcome of expression is most easily visualized after somite formation - Regional identity of the mesoderm is the result of a combination of Hox gene activities

Question 27

Hoxa clusters

Answer 27

* most anterior Hox gene - gene expression in cervical (neck), thoracic ( rib bearing), lumbar (non-rib bearing), sacral (attached to the hip bone) and caudal (tail)

Question 28

Hoxb clusters

Answer 28

* most anterior Hox gene | - gene expression in cervical (neck) and thoracic ( rib bearing)

Question 29

Hoxc clusters

Answer 29

* most posterior Hox gene | - gene expression in cervical (neck), thoracic ( rib bearing) and lumbar (non-rib bearing)

Question 30

Hoxd clusters

Answer 30

* most posterior Hox gene - gene expression in cervical (neck), thoracic ( rib bearing), lumbar (non-rib bearing), sacral (attached to the hip bone) and caudal (tail)

Question 31

Homeotic transformations (homeosis)

Answer 31

- the phenomenon in which one structure is transformed into another, homologous, structure as a result of a mutation - an example is the development of legs in place of antennae in Drosphila as a result of mutation - Piloted in mice - Homeotic transformation is when Hox genes expression can be removed or expressed in a different position and this is governing the identity of somite tissues - ex) taking the first lumbar vertebra and replacing it with a thoracic vertebra by changing Hox gene expression (Hoxc8)

Question 32

Hoxc8 deletion

Answer 32

- Is expressed in the thoracic and more posterior somites - Deletion in mice results in the first lumbar vertebrae developing into a 14th rib bearing vertebrae (an extra rib formed) formed through homeotic transformation - The 1st lumbar vertebrae takes on more anterior identity in the absence of Hox-c8 expression - This is an example of posterior dominance

Question 33

14th pair of rib structures

Answer 33

-a extra rib formed through homeotic transformation

Question 34

Posterior dominance

Answer 34

- Deletion in mice results in the first lumbar vertebrae developing into a 14th rib bearing vertebrae (an extra rib formed) - The 1st lumbar vertebrae takes on more anterior identity in the absence of Hox-c8 expression