EMBRYOLOGY 3

2009

Basic morphogenetic processes

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

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

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)

Zygotic genes are expressed in embryo (examples: segmentation genes – as gap, pair-rule, segment-polarity 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, Beckwith- Wiedemann 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:

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

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

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

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 region- induction of procencephalon development

Development of axial structure - notogenese

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

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

Primitive node and notochord – signal molecules – interaction between epithelial and mesenchymal cells

Regionalization – craniocaudal gradient -division of CNS (hox genes)

Neurulation

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

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

Axial mesoderm – notochord and cranial organizer (prechordal plate)

Intraembryonic mesoderm – Paraaxial – somites Intermediate Lateral: somatopleura, splanchnopleura and

intraembryonic coelom Cardiogenic field

Paraaxial mesoderm

Cranial reagion – somitomeres – swirls off cells in head region

Starting 8th somitomere they form somites

Somites (ED 20) – successive development

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

Vertebrae Intervertebrale discs Limbs Connective tissue

Dermatomyotome

Dermis Myotome –

Epaxial musculature Hypaxial musculature Muscle in limbs

Intermediate mesoderm

It joins somites and lateral mesoderm

Pronephros Mesonephros Metanephros

Cardiogic field

Blood islands Pericardiac cavity Endothelial tube

Malformation

Conjoined twins Syndrome caudal

regresion – sirenomelia

Sacrococcygeale teratoma

Situs inversus