Download INTRODUCTION TO EMBRYOLOGY

INTRODUCTION TO EMBRYOLOGY
Assoc Prof Dr E.Elif GÜZEL
Definition of Embryology
• The study of the developmental process from a single cell to a
baby in 9 months.
• In other words, investigations of the molecular, cellular and
structural factors contributing to the formation of an organism.
Human Development
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Development does not stop at birth!!
How does it start?
Zygote (totipotent cell)
Human
Transformation mechanisms include:
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cell division,
cell migration,
apoptosis,
differentiation,
growth,
cell rearrangement
Clinical Importance
• Understanding embryology is essential for creating health
care strategies;
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Prenatal diagnosis and surgical treatments
Therapeutic procedures for infertility
Mechanisms to prevent birth defects
Improvements in prenatal and reproductive health is significant for
improved birth
outcomes
postnatal long-term
effects
prenatal experiences effects cognitive
capacity and postnatal health
IMPOTANT FOR MOST PHYSICIANS
• Embryogenesis (organogenesis);
– Establishment of the organ primordia from a single cell
– The first 8 weeks of human development
• Fetal period;
– From 9th week to birth
– Differentiation and growth
– Fetus gains weight
• Trimester;
– 1/3 of the normal length of pregnancy
• Teratology;
– Study of the embryological causes for birth defects
• Genetic
• Environmental
Descriptive Terms in Embryology
• Spermatozoon= Sperm
• According to the anatomical position, the position of the
organs are described using some terms:
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Anterior/ventral
Posterior/dorsal
Superior/ cranial (or rostral)
Inferior/caudal
Molecular Regulation of Embryogenesis
• Progress in the field of molecular biology enhanced our
understanding of normal and abnormal development
• 23,000 genes…..150,000 proteins
Chromatin
• Chromatin: a complex of DNA and histone proteins
• Nucleosome: the basic structural unit of chromatin
• Nucleosomes keep the DNA tightly coiled, such that it
cannot be transcribed….heterochromatin
• DNA must be uncoiled to be transcribed…. euchromatin
Gene Transcription
Regulation of Gene Expression
**Transcription Factors
• Protein that binds to specific DNA sequences, and control the
transcription of genetic information from DNA to mRNA.
• Depending on the transcription factor, the transcription of the
adjacent gene is either activated or inhibited.
**DNA Methylation
• Methylation of cytosine bases in the promoter
regions of genes inhibits transcription of those genes.
• Some genes are silenced by this mechanism
– Muscle cells make muscle proteins not blood proteins
**Alternative Splicing
• Why different cells by using the same gene produce different
proteins?? A single gene may give rise to several proteins
• By removing different introns from pre-mRNA
• Splicing isoforms
Post-translational Modifications
• Activation of some proteins depends on….
– Combination with other proteins
– Phosphorylation
– Cleavage
Induction and Organ Formation
• How does organ formation occur???
Organs are formed by interactions between cells and tissues
One group of cells or tissues
causes another set of cells or
tissues to change their fate
INDUCTION
Inducer-Cell Signaling-Responder
Inductive Interactions Between Epithelial and
Mesenchymal Cells
• Epithelial cells join together to form tubes or sheets
• Mesenchymal cells are fibroblastic in appearance and dispersed in
extracellular matrix
• Although an initial signal from inducer to responder starts the inductive
event, crosstalk between two tissues or cell types is essential for
differentiation to continue
Examples of Epithelial-Mesenchymal Interactions
• Gut endoderm and surrounding mesenchyme…. gut
derived organs (liver, pancreas)
• Development of the kidney
Cell Signaling
• Essential for induction
• Established by signaling proteins (ligand)
• Receptor
– Spans the cell membrane
• Extracellular domain (ligand binding region)
• Transmembrane domain
• Cytoplasmic domain
• Action???
– Activating directly
– Blocking the activity of an inhibitor of a pathway
(inhibiting an inhibitor)
Typical Signal Transduction Pathway Process
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Ligand binds its receptor…..
Conformational change occurs in the receptor….
Cytoplasmic region gains an enzymatic activity (mostly kinase)….
Phosphorylation of some cytoplasmic proteins….
Activation of a transcription factor….
Activation or inhibition of genes.
Types of Signal Transduction Pathways
• Paracrine Signaling; proteins synthesized by one cell diffuse
short distances to interact with other cells
• Juxtacrine Signaling; does not involve diffusable proteins
Paracrine Signaling
• Diffusable proteins responsible
for the paracrine signaling are
called paracrine factors or
growth and differentiation
factors (GDFs).
• Uses typical signal transduction
pathway process.
Juxtacrine Signaling
1. A protein on one cell surface interacts with a receptor on
an adjacent cell
 uses typical signal transduction pathway process
 Notch signaling (neuronal and blood vessel differentiation,
somite segmentation)
2. Ligands in the extracellular matrix interact with their receptors
on neighboring cells (cells attach to or migrate on these ligands)
 Epithelial cells attach to laminin of basal lamina
 Fibronectin for cell migration
 Receptors are called integrins
3. Gap junctions
Paracrine Signaling Factors (GDFs)
• Regulate development and differentiation of organ
systems
• Grouped into 4 families;
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Fibroblast growth factor
WNT
Hedgehog
Transforming growth factor-β (TGF-β )
Fibroblast Growth Factors (FGFs)
• Originally named because they stimulate the growth of fibroblasts in
culture
• app. 25 different genes….hundreds of proteins
• Receptor tyrosine kinases (FGFRs)
• Important for;
– angiogenesis
– axon growth
– mesoderm differentiation
• e.g. FGF8 is important for development of the limbs and part of the brain
Hedgehog Proteins
• There are 3 hedgehog genes;
– Desert
– Indian
– Sonic hedgehog
• Sonic Hedgehog is important in
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Limb patterning
Neural tube induction or patterning
Somite differentiation
Gut regionalization
• Action on the receptor is inhibiting an
inhibitor
WNT Proteins
• Involved in regulating….
– limb patterning
– midbrain development
– somite differentiation
– urogenital differentiation
TGF-β Superfamily
• More than 30 members
– TGF-βs
• Important for extracellular matrix formation
• Important for epithelial branching that occurs in the
lung, kidney and salivary gland development
– Bone morphogenetic proteins (BMPs)
• Induces bone formation
• Regulates cell division, apoptosis, cell migration
– Activin familiy
– Müllerian inhibiting factor
Other Paracrine Signaling Molecules
• Two neurotransmitters important for embryological development
• Seratonin (5HT)
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Cell proliferation
Cell migration
Establishing laterality
Gastrulation
Heart development
• Norepinephrine
– Apoptosis in interdigital spaces
References
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The Developing Human: Clinically Oriented Embryology by Keith L.
Moore, T. V. N. Persaud and Mark G. Torchia (2013). 9th ed. Elsevier
Saunders, Philadelphia. ISBN: 978-0-8089-2444-9
Langman’s Medical Embryology by T.W. Sadler (2012). 12th ed.
Lippincott Williams & Wilkins, Philadelphia. ISBN: 978-1-4511-4461-1