Cellular Development PDF

Cellular Pathways in Embryology Cell Biology MED102 Prof A. Stephanou Objectives: Understand that developing embryo involves processes such as EMT and Differentiation Understand that different stages exist for growth: cleavage and formation of blastocyst Germ layers...

Cellular Pathways in Embryology Cell Biology MED102 Prof A. Stephanou Objectives: Understand that developing embryo involves processes such as EMT and Differentiation Understand that different stages exist for growth: cleavage and formation of blastocyst Germ layers important for the formation of all the tissue/organs Signalling / Morphogens crucial for embryo-fetus development Fertilization: The process in which the spermatozoon penetrates into the ovum to form fertilized ovum. In the ampulla of oviduct  Process of fertilization Sperm bind to sperm receptor ZP-3 induce Acrosome reaction：release of acrosomal enzyme Penetration and Cell release of acrosomal membrane nucleus acrosome enzyme of ovum  Process of fertilization ① Fusion of the ② The nucleus ③ Formation of ④ Fusion of membrane of of sperm pronuclei pronuclei penetrate into sperm and ovum ovum Alteration of ovum 24 h Significance of fertilization ① A new life ② Diploid ③ Sex determination  Prenatal Development Embryonic Fetal development development fertilization - 8 weeks 9 weeks - birth time period from fertilization to birth = gestation Postnatal Development: 1) neonatal, 2) infancy, 3) childhood, 4) adolescence, and 5) maturity. the first trimester is from week 1 to the end of week 12. the second trimester is from week 13 to the end of week 26. the third trimester is from week 27 to the end of the pregnancy  pregnancy is divided into trimesters: The first trimester is from week 1 to the end of week 12. The second trimester is from week 13 to the end of week 26. The third trimester is from week 27 to the end of the pregnancy  The first Trimester (weeks 1-12; fetus size ~ 3 in.; weight ~ 14 g) ⚫ Cleavage ⚫ Implantation ⚫ Placentation ⚫ Embryogenesis Phase of cleavage Fertilized 2-cell stage egg 18~36h 4-cell 8-cell stage stage 36~48h 48~60h  Morula 12 to 16-cell stage The third day Appearance and inner structure of blastocyst Appearance Inner structure  Cleavage Early division of zygote into multiple cells without increase in size, partitions contents Morula solid ball of cells Zygote Blastocyst with blastocoele cavity Implantation - embedding of blastocyst into uterine lining begins at day 7 Blastocyst - with blastocoele cavity Trophoblast - outer layer of cells Inner cell mass - will form embryo Trophoblast forms syncytial trophoblast- erodes into endometrium Cellular trophoblast - carries nutrients to inner cell mass Lacunae and primary villi formed by trophoblast All of these form placental tissues Implantation at 7th day Cytotrophoblast Inner cell mass Polar trophoblast Endometrium  Epiblast Columnar cells Bilaminar germ disc Hypoblast Cuboidal cells Epiblast Hypoblast 1.Bilaminar germ disk： Inner cell mass→2 layers of cell in disc (7th day) Epiblast: columnar cells adjacent to trophoblast Hypoblast: cuboidal cells adjacent to blastocoele 2. Amnion：8th day epiblast → amnioblast → aminiotic membrane → amniotic cavity → amniotic fluid 3.Primary yolk sac： 9th day hypoblast →extraembyronic endoderm →primary yolk sac Bilaminar germ disc at 9th day Primary yolk sac Hypoblast Epiblast Amniotic cavity Syncytio- trophoblast Embryo completely Day 10 embedded in endometrium Amnion and yolksac visible Blastodisc formation (2 cell layers) – Epiblast – Hypoblast  Formation of Extra-embryonic Membranes visible after day 10: Amnion – Protection of embryo/fetus Yolk sac – Early site of blood cell formation 4. Extraembryonic mesoderm: 10th-11th day 5. Extraembryonic cavity: 12th-13th day Extraembryonic mesoderm: visceral layer parietal layer 6. Secondary yolk sac: 13th day 7. Body stalk: 14th day Gastrulation: 3 Germ Layers Formed day 12: Ectoderm (forms from epiblast) Nervous system Epidermis Endoderm (forms from hypoblast) Mucosae (eg: GI-tract Associated glands Mesoderm Everything else  Formation of endoderm Epiblast Primitive streak Endoderm Hypoblast  Formation of mesoderm Epiblast Mesoderm Endoderm  Trilaminar germ disc Ectoderm Mesoderm Endoderm  Formation of trilaminar germ Trilaminar germ disc: Primitive Streak (primitive streak will establish bilateral symmetry, determine the site of gastrulation and initiate germ layer formation) primitive streak, primitive groove 3rd week primitive node, primitive pit 3rd week 1. Endoderm: primitive groove →hypoblast → endoderm 2. Mesoderm： primitive groove →between epiblast and hypoblat →mesoderm 3. Ectoderm：epiblast →ectoderm  Differentiation of trilaminar germ and formation of embryo 1. Differentiation of ectoderm Differentiation of trilaminar germ ①Neural tube：blastema of CNS neural plate (18th-19th day) Neuro-epithelium (neural ectoderm): pseudostratified columnar →neural groove , neural fold → neural tube (closed at 22nd day) ②Neural crest： blastema of PNS chromaffin cell, parafollicular cell some of bone, cartilage and muscle of head ③Superficial ectoderm: after formation of neural tube epidermis 2.Differentiation of mesoderm 17th day ①Paraxial mesoderm：somite at 20th day, from the head Dermotome→ dermis, hypodermis Myotome → skeletal muscle, Sclerotome → axial skeleton. ②Intermediate mesoderm：urinary and reproductive system ③Lateral mesoderm：parietal mesoderm， viseral mesoderm， intraembryonic coelomic cavity 3. Differentiation of endoderm Epithelium of primitive gut → epithelium of digestive tract, digestive gland, respiratory tract and lung Primitive pharynx →5 pairs of pharyngeal pouch Formation of embryonic body (4-8th week) 5th week: upper and lower limb buds 6th week: hand and foot plates 7th week: formation of face, disappear of somite (Somites are bilaterally paired blocks of paraxial mesoderm that form along the head to tail axis of the developing embryo) 8th week: breach of cloacal membrane (development of the urinary and reproductive organs) (cloacal membrane, the membrane ruptures, exposing the urogenital sinus and dorsal anorectal )  Fig Text from previous slide a, Timeline of human development from fertilization to birth. CT, cytotrophoblast; ESC, embryonic stem cell; EPI, epiblast; PrE, primitive endoderm; pcw, post-conception weeks; SCT, syncytiotrophoblast; TE, trophectoderm; TSC, trophoblast stem cell; XEN, extraembryonic endoderm; YSE, yolk sac endoderm. b, Models derived from human stem cells, and associated studies. In vitro model systems to study early embryonic development. A–P, anterior–posterior. c, Experimental model systems to study development, including Drosophila melanogaster, Danio rerio, Xenopus laevis, Gallus gallus, Mus musculus, cell culture and organoids, and their amenability to facilitating various aspects of scientific study.  Placentation It occurs after the implantation of the embryo into the uterine wall and involves the remodeling of blood vessels in order to supply the needed amount of blood. In humans, placentation takes place 7–8 days after fertilization Development of placenta from edges of blastocyst Placenta = organ that forms from the chorion and the endometrium and allow the embryo/fetus to exchange nutrients and waste. Chorionic villi provide surface area for exchange Nutrient and gas exchange happens without actual blood exchange Umbilical cord - contains two umbilical arteries and one umbilical vein  Embryogenesis Following gastrulation, formation of viable embryo Head fold and tail fold develop Critical period organogenes Teratogens, Teratology = ? Rubella and syphilis X-rays & Smoking  Second and Third Trimester ⚫ After the end of 8 weeks: Fetal development ⚫ Week 12: all organ systems laid out ⚫ Most teratogens not lethal anymore – but produce major defects ⚫ 3rd trimester mostly for size increase and maturity. Germ layer formation: from blastula to animal  Cell Specification ⚫ Commitment – Specification – Determination ⚫ Terminal differentiation  Cell Specification Terminal Differentiation ⚫ When a cell can no longer change or be changed into anything other than the cell type it is ⚫ Can be associated with permanent changes in DNA – Methylation is a prominent factor – B-cells (plasma cells) rearrange the immunoglobulin (Ig) genes so that they can now only form a single type of Ig  Conditional Cell Specification ⚫ Cell-Cell interactions – Inhibition by neighboring cells – Inductions ⚫ Neighboring cells initiate induction events – Morphogen gradients ⚫ Soluble molecules which diffuse from source cells and affect the differentiation of cells at a distance  Conditional Cell Specification Regeneration in flatworms is directed by an anteroposterior (A-P) morphogen gradient  What is the mesoderm-inducing signal? secreted factor act at a distance expressed by endoderm at right time (late blastula/gastrula stages) ectoderm competent to respond Finding the signal: expression screen: determine endoderm-specific transcripts 30+ years of screening: TGFβ and FGF signaling What is the mesoderm-inducing signal? Cellular Interactions: Patterning and TGFb superfamily signaling What is the mesoderm-inducing signal? FGF signaling pathway