Patterning The Vertebrate Body Plan Ii: The Somites And Early Nervous System

Front 1

All vertebrate embryos are similar at the _______ _______
Somites, notochord and neural tube show ______ organization.
Patterning turns ______into repeated structures of skeleton and trunk muscles.
Dorsal mesoderm during gastrulation is internalized to eventually become the ________ and the ________.

Back 1

phylotypic stage; A/P; mesoderm; notochord and the somites

Front 2

The notochord is transient & becomes part of ______ ______

Back 2

spinal column

Front 3

With _______, ectoderm overlaying the notochord forms the _______to give rise to _____ & spinal cord.

Back 3

neuralation; neural tube; brain

Front 4

Somites, mesoderm in blocks flanking notochord, become the ...
(3 things)

Back 4

1) vertebrae and ribs
2) muscles of the trunk and limbs and
3) contribute to the dermis.

Front 5

Neural crest cells migrate away from the neural tube to develop into... (3 things)

Back 5

1) skull (bone)
2) sensory and autonomic nervous systems
3) pigment cells

Front 6

In the chick, ______ forms anterior to the regressing node of the primitive streak.

Back 6

mesoderm

Front 7

Pre-somitic mesoderm is the region between .....?

Back 7

the last formed somite and the regressing node

Front 8

The position of somites along A/P axis determines ____.
Anterior somites form _______ vertebrate.
Posterior ones, ribbed_____ vertebrate.
Develop in a _______ and _____ order.

Back 8

fate; cervical; thoracic; temporal and spatial

Front 9

_______ pre-somitic mesoderm will not change the pre-established timing. Describe an experiment which suggests this.

Back 9

Rearranging. See Fig 4.4
The pattern is laid down earlier by an A/P axis signal.

Front 10

Define posterior dominance

Back 10

See Fig. 4.13. A general principle of hox gene expression is that more posteriorly expressed hox genes tend to inhibit the action of the hox genes normally exressed anterior to them; this means that a change in hox gene expression usually affects the most anterior regions in which the gene is expressed, leaving posterior structures relatively unaffected.

Front 11

Define Homeobox genes

Back 11

Homeobox genes are...
a large family of transcription factors.
Share a similar 60 amino acid DNA binding homeodomain which is encoded by 180 basepair homeobox sequence.
Homeobox gene family (transcription factor proteins).
Homeotic transformation is often observed in mutants of genes that have this domain. Identified first in Drosophila (Bithorax and Antennapedia complexes) as a split cluster.
There are four separate clusters of Hox genes (subset of the homeobox genes) in vertebrates.

Front 12

Define Hox genes (Hox gene clusters)

Back 12

Hox genes ( Hox gene clusters) are a subset of the homeobox genes of transcription factor genes.
Might have arisen by rounds of duplication of an ancestral gene, followed by a quaduplication of the cluster in mammals.
Paralogous groups are composed of the most similar members of each cluster.
Partially overlapping zones of expression which vary in the anterior extent of their expression define distinct regions.
Various genes respond to the combination of gene products expressed.
Most homeobox genes are not Hox genes (i.e. Pax genes)

See Fig. 4.9, Fig. 4.11, box 4A pg. 156

Front 13

The differences between vertebrate (i.e. anterior -attach to skull; cervical; thoracic have ribs; lumbar, sacral and caudal) clearly demonstrate what?

Back 13

that identity of somites differ along the A/P axis

Front 14

Describe how Hox genes are expressed along the A/P axis in mouse.

Back 14

First, anterior Hox genes expressed in early gastrulation as mesoderm begins to leave the primitive streak.
More posterior Hox genes turn on as development continues.
Defined patterns of Hox gene expression are seen in...
1) mesoderm (after somite formation) &
2) neural tube (neuralation).

Front 15

Hox genes show a sharp ______ border and a much less defined _______ border

Back 15

anterior; posterior

Front 16

Lot of overlap by every region (almost) has distinct set of Hox gene expression.
Most anterior somites express _______ and _____ only.
Posterior regions express ____ _____ _____.

Back 16

Hoxa1 and Hoxb1; all Hox genes.

Front 17

Hox gene expression is co-linear .... what does this mean?

Back 17

Hox gene expression is co-linear as order of genes on the chromosome (per cluster) reflects the order of spatial and temporal expression along the A/P axis.

Front 18

Somite formation in chic:
• ______ is made in the node and after cells leave the node it
is increasingly ______ resulting in a _______
• Similar situation for Wnt3a

Back 18

FGF-8; degraded; gradient

Front 19

Spacing of somite boundaries formed by what?

Back 19

Spacing of somite boundaries formed by FGF and Wnt
gradient

Front 20

Spacing of somite boundaries formed by FGF and Wnt
gradient
• When both Wnt3a and FGF8 fall below threshold level -
what happens?

Back 20

segmentation program activated

Front 21

Spacing of somite boundaries formed by FGF and Wnt
gradient
• When both Wnt3a and FGF8 fall below threshold level -
segmentation program activated
• If increase FGF8, block segmentation
• Changing slope of gradient by increasing or decreasing
Wnt or FGF results in a what?

Back 21

change in somite size

Front 22

• Somitic mesoderm produces
retinoic acid, which
________ FGF

Back 22

antagonizes

Front 23

• RA biosynthesis in somites
(_______ by FGF), RA
degradation enzymes
expressed at _______
(induced by FGF)

Back 23

repressed; posterior

Front 24

• Decrease RA (vitamin A
deficieny) does what to FGF?

Back 24

• Decrease RA (vitamin A
deficieny) increases FGF

Front 25

• Excess RA causes what?

Back 25

• Excess RA causes lack of
FGF

Front 26

somite A/P fate determined
before or after formation

Back 26

somite A/P fate determined
before formation

Front 27

Deletion of Hoxc8 gene in chick embro results in what?

Back 27

Lumbar----> thoracic
Posterior-anterior
“posterior dominance”

Front 28

What defines HOX expression pattern?

Back 28

RA directly affects Hox
genes:
Somitic mesoderm produces
retinoic acid, resulting in an
posterior to anterior gradient
within the somitic mesoderm
and rhombomeres of
hindbrain

Front 29

Describe the mechanism by which RA directly affects Hox
genes

Back 29

• retinoic acid receptors (RARs) which heterodimerize with retinoid
X receptors (RXR)
• Heterodimer acts as a transcription factor, binds to RARE
• In absence of Retinoic acid (orange) RAR interacts with corepressor,
negatively regulates transcription through deacetylation
• In presence of Retinoic acid (orange) RAR interacts with coactivator,
positively regulates transcription through acetylation
• Hox genes contain RARE (retinoic acid response elements)

Front 30

Describe ways in which Retinoic acid acts as teratogens (substances which disrupt embryonic development)

Back 30

• Vitamin A
• insecticides (methoprene = juvenile hormone
mimic - exposure to sunlight produces retinoic-like
breakdown product
• Accutane (acne drug) = Retinoic acid
• Women taking accutane
• 26 - normal
• 12 spontaneous abortions
• 21 abnormal births

Front 31

what are the most common types of malformations after RA exposure?

Back 31

Malformations to head are most common
after RA exposure

Front 32

Retinoic acid is a derivative of _______.
It has very important role in signaling _______ development.
In early development, retinoic acid can cause ______ ________ of the vertebrate.
It can diffuse across plasma membranes to bind protein receptors and form an active transcription factor.
Retinoic acid interferes with the ______ expression of Hox genes.
Later, it can alter positional development in limb development.

Back 32

vitamin A; vertebrate; homeotic transformation; normal

Front 33

Mesoderm becomes ______ and ______. The fate of somites depend upon ____ _____ _____.

Back 33

notochord and somites; adjacent tissues signals.

Front 34

Dermamyotome is dorsal & lateral somites (express Pax3) and becomes the ______ (forms muscle cells) and the _______ (an epithelial sheet that forms dermis).

Back 34

myotome; dermatome

Front 35

Medial somites (MyoD) forms axial & back _______.

Back 35

muscles

Front 36

Lateral region of somites form _______ and ________ muscles

Back 36

abdominal & limb muscles.

Front 37

Ventral medial region of the somite contain ______ ______ (future cartilage which express Pax1) and migrate to surround the notochord and form the ________.
Notochord _______ sclerotome cells.

Back 37

sclerotome cells; vertebrate; induces

Front 38

From notochord transplantation experiments, an additional notochord induces what?

Back 38

unsegmented pre-somitic mesoderm to produce greatly increased amount of cartilage
see fig 4.16

Front 39

In the mouse,what helps to pattern the A/P axis.

Back 39

FGF and retinoic acid gradients

Front 40

Desribe the hierarchy of induction which ltimately leads to segmentation in vertebrates (esp. mouse)

Back 40

1. D/V axis ----> A/P axis during
gastrulation
2. A/P axis ----> retinoic acid/FGF8 gradient
3. Retinoic acid----> A/P specific expression of
HOX genes + segmentation
4. HOX genes ----> transcription of segment
specific genes