Lecture 1_ Embryonic Development PDF

Why study development? ◦ Development of structures ◦ How normality arises ◦ How abnormality ensues ◦ Positioning of adult structures ◦ Understand that several tissues form at the same time, requiring same genes (e.g. Holt-Oram syndrome (HOS)) thus a defect in one tissue ca...

Why study development? ◦ Development of structures ◦ How normality arises ◦ How abnormality ensues ◦ Positioning of adult structures ◦ Understand that several tissues form at the same time, requiring same genes (e.g. Holt-Oram syndrome (HOS)) thus a defect in one tissue can indicate defects elsewhere Holt-Oram syndrome - heart/hand defects ◦ Atrial septation defects ◦ Range of hand abnormalities ◦ Phenotype due to mutation in one gene required at time both structures develop, thus knowing relationship of structure/organ development will aid in diagnosis Embryonic and foetal development ◦ Review of fertilisation ◦ Embryonic development ◦ Foetal development ◦ Organogenesis ◦ Placental functions ◦ Birth defects/abnormalities  Introduction ◦ Takes 9 months (40 weeks) for a human baby to develop ◦ 1st trimester - most important as this is when the body forms: ‣ Weeks 1-2 blastocyst stage ‣ Weeks 3-8 embryonic stage (organogenetic period) ‣ Week 9 - foetal stage ◦ 2nd trimester - rapid growth of foetus ◦ 3rd trimester - fat production and start of physiological processes Fertilisation ◦ In the fallopian tube ◦ Distal end 'ampulla' ◦ Sperm penetrates the several egg coats (acrosome reaction) ◦ Zona pellucida ‣ Prevents multiple sperm entry ‣ Permits implantation at appropriate site ◦ Fertilisation causes oocyte to complete meiosis; restores diploid number of chromosomes; determines sex (determined at conception) Fertilisation and implantation ◦ Takes 4 days to reach uterine cavity  Early human development ◦ Zygote = fertilised egg ‣ Size does not change even after cell divisions ◦ Morula to blastocyst: ‣ Ball of cells turns into a blastocyst ‣ Fluid released from cells ‣ Fluid collects beneath them ‣ Forms a cavity ◦ Inner cell mass gives rise to every cell in your body Twinning ◦ Two zygotes formed gives identical twins with separate placentas (A) ◦ Division of inner cell mass to form two inner cell masses gives identical twins with a shared placenta (B) ◦ If the inner cell mass is unsuccessful at splitting you will get conjoined twins (C)  Post-fertilisation ◦ Zygote = fertilised oocyte ◦ Travels down fallopian tube ◦ Divides = rst cleavage division (after 30 hours) ◦ Morula ◦ Blastocyst (when twinning can occur) ◦ Sheds zona pellucida ◦ Implantation ◦ hCG production (used to detect pregnancies) The bilaminar disc (approximately 9 days) ◦ Fluid released from inner mass, forcing them down into the middle of the blastocyst ◦ Two layers of cells form: ‣ Epiblast - gives rise to every cell in body ‣ Hypoblast - gives rise to yolk sac ◦ Syncytiotrophoblast invades uterine cavity to allow implantation of the embryo and also the formation of the placenta Blastocyst to foetus ◦ By 3 months, foetus is fully formed ‣ Just growth and expansion of existing tissues from this stage  How to make an embryo/foetus ◦ Gastrulation (produces 3 germ layers; helps to turn bilaminar disc into a 3D structure) ◦ Germ layers produced (ectoderm, mesoderm, endoderm) ◦ Notochord = structure that induces CNS to form ◦ Neurulation ◦ Neural crest migration = forms parts of the head ◦ Somitogenesis = forms vertebral column ◦ Axis elongation ◦ Folding and cavitation ◦ Organogenesis Gastrulation ◦ Day 15/16 a groove forms on the epiblast surface = the primitive streak (establishes anterior- posterior (A-P) axis of developing embryo) ◦ Extends from caudal (bottom) region of bilaminar disc gradually up to cephalic region of disc - the primitive node (= the organiser) ‣ Induces cells on the epiblast to move towards it and to move into the primitive streak and go inside and underneath the primitive streak to form three germ layers ◦ As the node and streak extends, cells from epiblast migrate into the streak to form endoderm and mesoderm Formation of a trilaminar embryo: gastrulation ◦ Buccopharyngeal membrane becomes future mouth ◦ Blastocyst becomes a shield-like structure Gastrulation and germ layer formation ◦ Mesoderm in the middle ◦ Endoderm sits on top of the hypoblast ◦ Epiblast replaced by ectoderm cells  Expansion of bilaminar disc ◦ Expands rapidly ◦ Cells moving in under control of the node ‣ Migrate towards head region ◦ One of the rst tissues to form is the notochord cells ‣ Form directly underneath the epiblast ‣ Move towards buccopharyngeal membrane ‣ Important role in inducing overlying ectoderm to become neural ectoderm to form the neural tube Progression of gastrulation and neurulation and expansion of embryonic disc ◦ 15 days - bilaminar disc ◦ Buccopharyngeal membrane = precordal plate ◦ Neural ectoderm makes the neural plate ◦ By 21 days, the primitive streak regresses, going back towards the bottom of the embryo where it came from ◦ Notochord running the length of the embryo ◦ Neural ectoderm starts to overgrow ◦ Notochordal process is in the mesoderm  Gastrulation and germ layer formation Gastrulation results in 3 germ layers ◦ Once gastrulation is nished, embryo is still at ‣ No inside ‣ Three layers of cells that have di erent fates ◦ You see as development proceeds the endoderm in the middle ‣ Endoderm - internal organs ‣ Ectoderm - skin and neural tube ‣ Mesoderm - blood, muscle and limbs ‣ Each edge of the ectoderm will move inwards and meet in the midline The endoderm will then be in the middle  Fate of the germ layers ◦ Vertebrate embryo ◦ Still at the point in human development where you are a at layer of tissue Neural tube formation (neurulation) ◦ Ectoderm is induced via notochord/mesoderm to become neuroectoderm ◦ Neuroectoderm gives rise to neural plate, neural groove and folds and ultimately to the neural tube ◦ Failure of this process leads to spina bi da ◦ Neurulation begins around day 19, and ends by day 27/8 with closure of posterior neuropore ‣ Last part of the nervous system to close over fully Neurulation produces the neural tube (CNS) ◦ Notochord inducing the overlying ectoderm to become the neural plate ‣ Use molecules such as bone morphogenetic proteins and Wnts ◦ Neural crests present to the side of the neural plate ‣ Named due to neural plate over-proliferation and forms folds ‣ Folds meet in the midline ‣ At the midline, neural crest cells are then at the crest of the neural fold ◦ As the folds merge, you get wound healing of the ectodermal layer to cover up the neural tube - now protected by skin ◦ Neural crest cells migrate ◦ Zipping up = process where the neural folds over-proliferate and meet in the midline  Neural crest ◦ Arise from crest of neural folds ◦ Migrates from neuroectoderm into underlying mesoderm ◦ Give rise to a whole host of tissues including: ‣ Melanocytes ‣ Glial cells and Schwann cells ‣ Cranial nerves ‣ Odontoblasts ‣ Connective tissue and bones of the face and skull ◦ Without neural crest cells, you will develop birth defects Somites ◦ Form on either side of neural tube from paraxial mesoderm ◦ Made up of 3 parts: ‣ Sclerotome - cartilage/tendon/vertebral column ‣ Myotome - muscle precursors ‣ Dermatome - skin precursors ◦ First somite appears day 20 ◦ Form anterior to posterior as the axis of embryo elongates ◦ By day 30, there will be 35 somites ◦ Related to vertebral column - give rise to each of the di erent vertebrae in your back ‣ Also produced muscle, skin, cartilage, and tendons that form the connections to the vertebral column ◦ Somites form as neurulation is occurring ‣ Somite blocks start to form either side of the notochord ‣ Allows the nervous system and the neural tube to be kept in a straight line and give them support Summary of early development  Neurulation sets up CNS ◦ Neural plate over-proliferation ◦ Folds start to move together and close over the midline ◦ Somites start to form ◦ Somites support the closure of the neural tube Closure of neural tube creates body axis ◦ By day 22, closure of the neural tube in the midline ◦ Somites packed together very tightly ◦ Head and tail are still undergoing neurulation and a bit of gastrulation ◦ Otic placode forming - future ear ◦ Pericardial bulge - future heart ◦ Formation of other tissues ◦ By day 23, you have an almost fully formed axis ◦ CNS fully enclosed inside and forming the spinal cord ◦ Somites neatly stacked and supporting the formation of the CNS ◦ Anterior and posterior neuropores still open - anterior neuropore is one of the last to close over  Neurulation is followed by lateral plate folding ◦ By day 19, the notochord induces the neural plate and the neural folds start forming ‣ Paraxial mesoderm forming - starts to produce somites ◦ By day 20, you have a neural groove, the folds are overgrown and about to meet in the midline, somites are starting to form and it is still very at ◦ By day 21, you have a neural tube where the folds have met in the midline with the ectoderm above it which is healed over, somites forming either side of neural tube to keep it straight, intermediate mesoderm forming (makes kidneys), also have the lateral plate which will go on to make the limbs ‣ Still at ‣ Ectoderm has started to move down - moves all the way down and meets in the midline Pinches o the rest of the yolk sac - endoderm now in the middle of the embryo Formation of the head- and tail-folds ◦ Tucks the developing heart and pericardial sac (cranial coelum) ventrally ◦ Pinches the gut tube o from the yolk sac and narrows the body stalk ◦ Head starts to bow down and tail fold bows inwards ‣ Pinches o the yolk sac ◦ Umbilical cord forms where the embryo connected to the uterus ◦ Connecting stalk created when the embryo is implanted into the uterus ◦ Connecting stalk is future umbilical cord ◦ Small opening for umbilical cord when the body closes ‣ Fully enclosed embryo ◦ Lateral plate folding - causes 3D cylinder  Lateral body folding ◦ Turns the embryo disc (body) into the cylinder instead of a sheet ◦ Rolls up the gut tube and nips it o from the yolk sac ◦ Means that the amniotic cavity surrounds the embryo except at the body stalk (forms the umbilical cord) Folding creates the embryo Folding creates the 3D embryo - gastrulation and neurulation continue until day 28 ◦ By day 28, both the anterior and posterior neuropores have closed over