SUBJECT
Mammalian-Human Histo- and Organogenezis I – II
lecture + practical
master
2 + 2
Semesters 1-4
Autumn/Spring semester
Lectures:
1. Introduction – Summary of mammalian morphogenesis, germ layers and their derivatives (mesodeum, somites, lateral mesoderma, head mesoderma, neural plate, neural crest). Signalization pathways in cell determination: Wnt, Notch-Delta, TGF, hedgehog.
2. Pattern formation, secondary induction - interaction between epithelial and mesenchymal tissues. The common steps in the formation of parenchymal organs: generation of branches in the insect tracheal system, the mammalian kidney and airway system.
3. Hox-genes – pattern formation along the antero-posterior axis, RA in developmental malformations. Morphogenesis of the mammalian viscerocranium: pharyngeal pouches, determination of the polarity, position and identity of the branchial arches (Bmp-7, Fgf-8, Pax1 and Shh expression). Interaction between the neural crest cells and the head mesoderm: the Hox and Dlx pattern.
4. Myogenesis – the Shh, Myf5 and MyoD in the skeletal muscle progenitor specification. Formation of the limb muscles: migration from somite, proliferation, determination and differentiation (effects of myogenin, MRF, Pax, Hox, Lbx genes). Proliferation or differentiation: the Notch and Hoxa genes.
5. Skin, epidermis formation – Establishment and stratification of the skin epithelium: stem cells; pattern formation: determination of the follicular and interfollicular epidermis, formation and morphogenesis of hair follicle; the hair follicle cycle: anagen, katagen, telogen stages; signaling and stem cell fate specification: Wnt, Shh, BMP, and Notch.
6. Skeletal system – a) Chondrocyte phenotype: collagen type II, collagen type X, aggrecan, SOX and COL genes; the role of BMP2, SOX9 and noggin in chondrogenesis. b) Bones: the role of TGF, BMP/OP in the osteogenesis, relationship between the angio– and osteogenesis.
7. Alimentary canal 1. – Foregut: morphogenesis of the teeth, modulating the number, shape and size of teeth (BMP and Barx genes). Antero-posterior patterning of the gut: transcription factors in the early gut tube. Development of the lung bud, stomach, duodenum, liver and pancreas; epithelium/mesenchymal interactions in the development (Nodal, Gata, Sox, Foxa).
8. Alimentary canal 2. – Growth and differentiation in developing organs. Stem cells in the small intestine, cell differentiation in the epithelium in villi and crypts of Lieberkühn, signaling pathways (Wnt, TGF, BMP, Ras, Notch, Shh, and Ihh).
9. Respiratory system – Morphogenesis of the airways and the lung, development of the type I and II cell (pneumocytes). Epithelial/mesenchymal interactions (FGF, Shh, Hip1, Gli, Wnt, BMP4, noggin, gemlin, RA). Resident stem/progenitor cells in the lung: submucosal glands, Clara cells, II type pneumocyte. Composition of the surfactant layer, characterization of SP proteins. Surfactant secretion and turnover, exocytosis of lamellar bodies.
10. Circulatory system, heart – cardiogenic commitment: GATA4, Nkx2.5, Tbx5, Hand1, 2. Cardiac morphogenesis and left-right asymmetry: Shh, Nodal, Zic3. The role of neural crest derived cells during cardiogenesis: Fgf8, Tbx1, and Islet1. Endocardium and cardiac valve formation: NFATc, Smad6, Notch1. Formation of the epicardium, epithelial/masanchymal transformation of the transversal septum: Fog2, GATA4.
11. Urinary system, kidney – steps of the morphogenesis. Formation and separation of the nephrotome from paraxial and lateral mesoderm, appearance of epithelial structures: BMP2 and Lim1, Odd1, Pax2/8 expression. Induction of uretheric bud outgrowth: Ret/Gdnf signals. Anterior-posterior-patterning genes affect the position of the metanephric mesenchyme: Hox11, Eya1, Six1, Wt1. Conversion of the metanephric mesenchyme to polarized epithelia: Wnt4/6/1. Induction of nephrogenesis: role of the Wnt4 in the cell aggregates, effect of Jnk in the transition of mesenchyme to epithelia, polarization. Development of glomeruli, changes in glomerular basement membrane, maintenance of podocyte differentiation ( Lmx1b). Role of the nephrin complex (nephrin, podocin, CD2AP, Neph1) in the integrity of the filtration barrier.
12. Genital system – Sexdetermination: Sry, Dss, Wt1, SF1, Sox9. Hox genes in developing genitalia: Hoxd13, Hoxa10/13, Shh, BMP4.
13. CNS – Formation of the embryonic brain (prosencephalon, mesencephalon, metencephalon), expression of Emx1/2 and Otx1/2 genes. The neuromer theory, role of the midbrain/hindbrain boundary (Wnt1, En1/2). Formation of rhombomeres: Hox genes.
Ventrally emigrating neural tube (VENT) cells and their fates in the developing peripheral nervous system and a variety of non-neural structures.
14. Sensory organs, eye – morphogenesis of eye: optic vesicle, appearance of the lens placod and cornea, defining axes within the developing eye. Role of the anterior neural plate in the eye induction (Wnt signalization). Generating two eyes: the cyclops (Cyc) gene and the hedgehog. FGF, BMP and activin in the retinal development. RA in establishing the dorso-ventral axis of retina. Lens induction: Pax6, BMP4/7, Sox1/2/3, fork head, Maf genes.
Exercises:
1. Basic histology – epithelium: single, stratified and pseudostratified epithelia, endo- and exoepithelial glands, types of morphology and secretion.
2. Basic histology – connective tissues: extracellular matrix and cells in embrional (mesenchymal and mucous connective tissue (Wharton's jelly)) and differentiated connective tissues (reticular, spinocellular, loose/areolar and dense). Adipose tissue.
3. Basic histology – cartilage (hyalin and elastic) and osseous tissues. Smooth muscle, myoepithelial cells. Neuron types, myelinization. Glial cells in the peripheral and central nervous system.
4. Integument/skin – Cells and layers of epidermis, structures of dermis/cutis and subcutis, vascularization of skin. Appendices and glands of skin (hair follicle, sebaceous and sweet glands). Free nerve endings and sensory corpuscles of skin.
5. Locomotory system – types and regulation of ossification, tendons and skeletal muscle.
6. Alimentary canal 1 – histology of the forgut: mouth cavity, salivary glands, tongue, tooth, esophagus, stomach.
7. Alimentary canal 2 – structure of the intestine, histology of the liver and pancreas. Hindgut and faces formation. Structural bases of peristaltic movement.
8. Consultation.
9. Respiratory system – embryonic lung, histology of differentiated airways: larynx, trachea. Lung: intrapulmonal airways and alveolar system.
10. Circulatory system – Examination of some steps of cardiogenesis. Types of blood vessels. Lymphoid organs: lymph node and spleen. Quantitative examination of blood, identification of cell types.
11. Urinary system – Histology of mammalian kidney, correlations between its structure and function. Bases of the urine formation, hormonal and neuronal regulation. Histology of the urinary tract: ureter and urinary bladder.
12. Genital system – histology of the ovary, maturation of follicles, development of oocytes, hormonal regulation. Structure of oviduct (Fallopian tube) and uterus, examination of vaginal smear. Histology of testis (steps of spermatogenesis), epididymis, vas deferens, seminal vesicle and prostate: structure, function and hormonal regulation.
13. CNS – embryonic CNS, neurulation, formation of the brain. Observation of Rexed laminae in spinal cord on Nissle stained slides. Examination of slides from neocortex, hippocampus and cerebellum. Structures of meninges and choroid plexus.
14. Sensory organs – Sensory perception: sinus hair, taste buds. Histology of the inner ear and the eye: retinal layers and lens structure.
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Thomas W. Sadler: Langman's Medical Embryology. Lippincott Williams & Wilkins, 2006
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Michael H. Ross, Wojciech Pawlina - Histology: A Text and Atlas. Lippincott Williams & Wilkins, 2006