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Summary Human Embryology and Developmental Biology - Lecture 7 [Molecular Development]
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Human Embryology and Developmental Biology - Lecture 7 [Molecular Development]
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Human Embryology and Developmental Biology – Lecture 7: MolecularDevelopment (22-03-2018)
Molecular aspects of embryonic development:
Molecular techniques used in the modern field of experimental embryology
on BlackBoard, will be a part of the exam!!
Molecular aspects of gastrulation (left-right asymmetry), neurulation and
organogenesis
Example of organogenesis: limb development: morphogenic control of initiation, axial
determination and early limb development.
Molecular aspects of gastrulation:
Step 1. Wnt (signaling) activity is confined to the future posterior part of the embryo,
where it induces the expression of Nodal.
So wnt induces the expression of Nodal at the posterior end.
In the anterior part, the Nodal concentration will be lower than in the posterior part;
Step 2. The anterior visceral endoderm produces Lefty and Cerberus-like, which
will inhibit Nodal activity in the anterior end of the embryo.
Low Nodal-concentration in the anterior end and high Nodal concentration in the
posterior end.
The Wnt-signaling is a prerequisite for the gastrulation to kick in;
Wnt signals establishes a posterior signaling center, inducing the formation of the
primitive streak (becoming the organizer region) and the mesoderm.
Nodal – posterior
Lefty – anterior.
Prechordal plate is also known as the head organizer.
Step 3. As the primitive streak elongates, migrating cells of the epiblast join the tip of
the streak and a dynamic mass of cells form the primitive node at the tip of the
primitive streak.
Step 4. The primitive node expresses many genes, such as chordin, goosecoid
and hepatic nuclear factor-3B (HNF-3B).
These genes have an influence on transcription factors (transcription factors are in
blue on the slide).
e.g. transcription factor in the prechordal plate; Otx-2 and Lim-1. Knocking down
Lim-1 (and/) or OTX-2 will lead to no formation of the head.
Goosecoid and HNF-3B work together and are very important in formation of
the notochord.
, Goosecoid and HNF-3B are also important in body axis formation/neural
induction
T-genes are important for movement of epiblast cells from the primitive streak.
Epiblast cells that dive inward and form all three germ layers.
- Requirement of Lim1 in head organizer function.
o Knocking down Lim-1 generates headless mice.
Transcription factors are important for specializations and determinations of certain
areas.
Molecular aspects of left-right asymmetry:
- Up to gastrulation, the embryo is bilaterally symmetrical, but at that time
mechanisms start to organize the left-right asymmetry
- Two recent models show that differences in ciliary currents at the primitive
node may lie at the basis of the L-R asymmetry.
Lefty-1 expressed along the left side of the primitive streak, may prevent diffusion of
molecules to the right side.
As a consequence: Sonic Hedgehog (SHH) and fibroblast growth factor-8 (FGF-8)
are sweeped toward the left side of the embryo.
Stimulation of nodal at the left side.
A sequence of molecular interactions, downstream of Nodal, results in the activation
of Pitx-2 (transcription factor).
The Pitx-2 protein leads to the asymmetrical development (e.g. the right-sided
looping of the heart, the asymmetrical looping of the gut and the asymmetrical
positioning of the liver, spleen and lobation of the lungs).
Sometimes, Lefty-1 expression does not occur at the left, but on the right side
Clinical condition: situs inversus. This results in the left-right asymmetry of the body
being totally reversed.
Only by making an x-ray it can be discovered that you have situs inversus. Situs
inversus has no severe consequences.
Kartageners syndrome: results from immotile cilia, is associated with situs inversus
but this syndrome causes respiratory symptoms.
Dextrocardia: isolated right-sided heart. Partial situs inversus will result in lots of
ventricular problems.
SHH is first expressed in the notochord and later SHH is also expressed in the
floorplate and induces ventral differentiation in the neural tube.
Overlying ectodermal structures secrete BMP.
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