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: s egmentation 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 c ranio-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 - 3 rd 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(3 rd 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.