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Transcript
EMBRYOLOGY 3
2009
Basic morphogenetic processes
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Processes which are involved in development
Proliferation – mitotic division - growth
Apoptosis – reduction of cell number (neurons,muscle),
formation of organs as hand, liquidation of organs (tail,
Mullerian and Wollfien ducts)
Association – cells express intercellular junctions, coordination
Migration – loss of intercellular contacts – cells express
adhesive molecules for attachment to the intercellular matrix
Induction → determination (cells obtain information and express
transcriptional factors), signal molecules) and differenciation
(cells change their structure)
Regulatory genes
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Transcription factors – specific proteins, their
attachment to DNA allows expression of
genes – typical for certain types of cells or
stages of development – beginning of
developmental cascade or network –
intracellular signal transduction pathway
Intercellular signaling molecules – growth
factors
Receptors for signaling molecules are also
needed
Cascade of regulatory genes
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Maternal effect genes – present in oocyte, allow to
recognize the beginning of cascade, enviroment for
right expression of genes, (in Drosophila they
determinate antero-posterior axis, germ cells) in
mammals they allow to start (they code m-RNA, and
proteins present in oocyte)
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Zygotic genes are expressed in embryo (examples:
segmentation genes – as gap, pair-rule, segmentpolarity genes; and homeotic (Hox) - they are
transcriptional factors
Imprinting
Imprinting is present only in placental mammals.Some
genes are inactivated (methylation) during formation
of gamets and they are activated according to their
origin (father, mother). Not randomly. It isd important
for early development.
Paternal genes are necessary for fetal membrane
development (disturbance - molla)
Maternal genes are necesary for embryo
development (disturbance - ovarial teratoma).
Contiguous gene syndromes: Prader-Willi sy (deleted
paternal chromosome 15), Angelman sy, BeckwithWiedemann sy (mother)
Signaling molecules: morphogenes
Morphogenes are signalling molecules which affects development.
They are present in extracellular space
Wnt (wingless) - proliferation
TGF-β - differentiation
Hedgehog (Shh, Ihh,Dhh) – concentration gradient –
structuralization of space
Notch – lateral inhibition - cells are not allowed to
differentiate in the same time, it allows organs to growth
Toll/dorsal - concentration gradient for formation of dorsoventral axis
Signal molecules:
Transcriptional factors:
Hox genes – are activated and expressed according to a strictly
sequence in clusters for cranio-caudal segmentation of the
body
Pax genes – development of CNS, senses and epithelial cells
Sox genes
Other – Lim
Growth factors: FGF, BMP4
Cell receptors -receptor kinases (tyrozin, serin-threonin)
Embryonic axes:
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Antero-posterior
Embryonic and vegetative pole
Left-right
Dorso-ventral
Cells are determinated for different structures
of the body
Fate map
Development of embryoblast –
gastrulation - 3rd week
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Development of 3 germ layers: ectoderm,
mesoderm and endoderm
Proliferation of epiblast – formation of
primitive knot and primitive streak
Cell loose their intercellular junctions
They change shape - bottle cells
They start to migrate inbetween epiblast and
hypoblast forming 3 layers. Hypoblast
undergoes apoptosis.
Gastrulation
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Mesoderm(3rd layer) consists from:
Notochord
Paraaxial mesoderm
Intermediate mesoderm
Lateral mesoderm
Gene expression and cell morfology are
transformed, relationship to the extracellular matrix
(hyaluronic acid, fibronectin)
Notochord
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Axial structure
It produce signals – induction of changes in
ectoderm – neuroectoderm and ventral plate
of neural tube, in mesoderm – somites and
in endoderm = segmentation
It grows from primitive streak to the
oropharyngeal plate (prechordal plate)
Prechordal plate = organizer in head regioninduction of procencephalon development
Development of axial structure
- notogenese
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After notochord has reached oropharyngeal
membrane, it grows by proliferation and
migration of cells of primitive streak and
node – caudal morfogenetic system
After head and neck has formed, body grows
by the activity of caudal morfogenetic system
Primitive streak breaks down or reduces
gradually
Sacrococcygeal teratoma
Development of notochord
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Tubular process –opening – cells form plate
Junction of primitive node and yolk sac –
neurenteric canal
Separation from neighbourhood – definitive
notochord – solid rod
Induction of neuroectoderm
development
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Primitive node and notochord – signal
molecules – interaction between epithelial
and mesenchymal cells
Regionalization – craniocaudal gradient division of CNS (hox genes)
Neurulation
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Neural plate – restriction, determination and
differenciation of ectoderm (under the control of
notochord)
Cell proliferation – neural groove, neural folds
Folds fuse – it starts in cervical region and continues to
the cranial and caudal end – cranial and caudal
neuropores
Rest of cells = neural crest - cells forming neural tissue
in periphery, melanocytes, ectomesenchyme in cranial
reagion etc.
Neural tube segmentation
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Division of brain - 3 brain vesicules –
prosencephalon, mesencephalon and
rhombencephalon
Segments – neuromeres
Mechanism: segmental genes are
expressed (hox)
Segmentation of neural tube – induction signals for paraaxial mesoderm
Segmentation
Embryo segmentation is organized according to time and space
rules. Formation of new pairs of somites and their number are
under the control of molecular clock. Their nature is the
periodic expression of specific genes (FGF and Wnt).
FGF and Wnt stimulate proliferation of mesenchymal cells.
Other signal molecules - Notch (it prevents differentiation of
neighboring cells). If cells express FGF and Notch, they can
proliferate. Later they express Wnt and they are changed into
epithelial cells. Differentiation is also under the control of
retinoic acid
Mesoderm
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Axial mesoderm – notochord and cranial
organizer (prechordal plate)
Intraembryonic mesoderm –
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Paraaxial – somites
Intermediate
Lateral: somatopleura, splanchnopleura and
intraembryonic coelom
Cardiogenic field
Paraaxial mesoderm
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Cranial reagion –
somitomeres – swirls
off cells in head region
Starting 8th
somitomere they form
somites
Somites (ED 20) –
successive
development
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4 pairs occipital
8 pairs cervical
12 pairs thoracal
5 pairs lumbal
5 pairs sacral
3 pairs coccigeal
Somites are divided into the cranial and caudal
part, then into ventral and dorsal part.
Ventral part is changed back into mesenchyme –
sclerotome. Dorsal stays as epithelium –
dermatomyotome, cells of it get to divide into
superficial dermatome, and underlying - myotome.
Sclerotomes develop in bone and cartilage of vertebrae
and ribs. Sclerotome divides into rostral and caudal
segment. Neighboring segments of somites fuse
together forming vertebrae. It results in the shift
allowing connection between nerve and skeletal
muscle
Some cells from the sclerotome migrate on the border
between future vertebrae forming tendon - progenitor
cells - syndetome.
Sclerotome
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Vertebrae
Intervertebrale discs
Limbs
Connective tissue
Dermatomyotome
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Dermis
Myotome –
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Epaxial musculature
Hypaxial musculature
Muscle in limbs
Intermediate mesoderm
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It joins somites and
lateral mesoderm
Pronephros
Mesonephros
Metanephros
Cardiogic field
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Blood islands
Pericardiac cavity
Endothelial tube
Malformation
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Conjoined twins
Syndrome caudal
regresion –
sirenomelia
Sacrococcygeale
teratoma
Situs inversus