VM1038 Week 3 Session 2 Embryological Development - Tagged.pdf

Embryological Development and Organ systems VM1038 Where opportunity creates success Learning Outcomes • Outline basic embryological development • Describe the development of the mammalian embryo from fertilisation to differentiation into endoderm, ectoderm, and mesoderm • Describe the relationsh...

Embryological Development and Organ systems VM1038 Where opportunity creates success Learning Outcomes • Outline basic embryological development • Describe the development of the mammalian embryo from fertilisation to differentiation into endoderm, ectoderm, and mesoderm • Describe the relationship of organs and tissues to their embryological origin • List the organ systems of generic mammal species Organ • Possible that the word relating to music preceded anatomical use • “Organ of speech” about the same time as bodily organs • Anatomy recognised since people started banging rocks together • Anatomy as a discipline 300 yr BCE • Anatomy dominated understanding of organisms as physiology poorly understood • Circulation of blood – William Harvey 1628 (helped by a vet though!) • To an extent we are still dominated by an anatomical approach to organ systems – hospital departments for instance Organ Systems • Nervous System • Integumentary System • Cardiovascular System • Musculoskeletal System • Respiratory System • Haematopoietic System • Digestive System • Immune System • Urinary System • Endocrine System – Group of unrelated organs – Secrete direct into blood stream • Reproductive System Organ Systems are not isolated • Obvious, but needs to be said • Organs do not and cannot exist in isolation • They are part of a whole organism • Rare that an organ will – Have a single isolated action – Have an action that wasn’t influenced by another homeostatic process • Organ systems can be a convenient way to study – But easy to get stuck in silos, “ let’s learn endocrinology!” • One of the reasons we teach in linked themes From Zygote to Organ systems • Another complex subject we need to condense • Understanding of embryo development helps with – Explaining developmental disease – Explaining failure of pregnancy – Need for correct nutrition in pregnancy/egg development – Roles in epidemiology – Explaining risk of treating pregnant animals – Understanding risks to self if planning pregnancy – (work related risks) • Examine stages from fertilisation to start of nervous system • A lot is based on human embryology Fertilisation • Ovum – Outer – Cells of corona radiata – Zona Pellucida- glycol protein – Inner Membrane (normal cell membrane) – Cell contains mitochondria, nucleus Fertilisation • Spermatozoa – Possess mitochondria and nucleus – DNA – Highly motile – Penetrates corona cells, ZP and membrane – Single spermatozoa only • ZP and membrane change to prevent entry of more – Acrosome reaction • Spermatozoa binds to cell membrane • Ovum and Spermatozoa nuclei fuse Sex Determination • Mammals – XX – Female – XY – Male – Y is only produced by males • Birds – ZW – Female – ZZ – Male – W is only produced by females • Reptiles – Some determined by temperature – An issue with global warming Cleavage and Morula formation • Fused nuclei – Now a zygote • Starts division = cleavage • All within zona – no increase in size • 2 daughter cells • 4 blastomeres • 8 blastomeres • 16 blastomeres • 32 blastomeres - morula • Note, sometimes it isn’t even numbers! Compaction • At the 8 cell stage • Cells change shape to maximise contact • Blastomeres move – Some central – inner cell mass embryoblast – Some periphery – trophoblast – placenta • Morula absorbs fluid – creates cavity – blastocoel • Blastocyst “hatches” from zona Early blastocyst • The structure enabling the embryo to implant is the blastocyst. • Consists of: • An outer epithelium- Trophoblast (part of the placenta/extraembryonic membrane). • An Inner Cell Mass- Embryoblast (will become the embryo. • The zona pellucida (ZP) will shed to allow blastocyst to increase rapidly in size and derive nourishment from secretions of the uterine gland. • Removal of the zona pellucida also known as ‘hatching’ enables implantation of the blastocyst. (will degenerate to allow implantation) (will become the placent Or Inner Cell Mass (ICM) – will become the embryo Cross-section of a blastocyst, showing blastocoel (blastocyst cavity), trophoblast and inner cell mass. Becoming bilaminar • Embryoblast splits into 2 layes – Epiblast – Hypoblast • Amniotic cavity develops – Thin layer of cells becomes amnion • Epiblast and Hypoblast – Become bilaminar disc – Sit between amniotic cavity and blastocoel • Trophoblast develops within uterine wall to become placenta Week 2- the ‘week of twos’ • Blastocyst implants into uterine wall. • The outer trophoblast differentiates into two layers: 1. Cellular layer of Cytotrophoblast (both light and dark green in diagram). 2. Syncytial layer of Syncytiotrophoblast • The Syncytiotrophoblast is highly invasive with active finger-like processes which expands rapidly into the maternal tissue. • Outer trophoblast layer becomes the interface between the embryo and he mother = placenta Week 2- the ‘week of twos’ Bilaminar germ disc • The embryoblast (ICM) differentiates into two layers: the Epiblast and the Hypoblast. – These two layers gives rise to germ layers that will contribute to embryonic and extraembryonic structures. – forms a flat disc. • Epiblast (tall columnar cells): – Pluripotent cells on ‘outer’ layer. These cells give rise to the embryonic tissue gives rise to the body structures and organs. – Floor of amniotic cavity. Dorsal Ventral Week 2- the ‘week of twos’ Bilaminar germ disc • Hypoblast (small cuboidal cells): – Transforms the blastocyst cavity/ blastocoel into the yolk sac. – Gives rise to extraembryonic tissues. Dorsal Ventral Becoming Trilaminar - gastrulation • Primitive streak develops in epiblast – At end that will become caudal • Cranial end expands as primitive node – Containing primitive pit • Primitive pit extends length of primitive streak – Primitive groove • Cells invade hypoblast • Differentiates into 3 layers Gastrulation • Creation of three germ layers – Ectoderm – Mesoderm – Endoderm • These layers give rise to all tissues and organs • Orientation – Body axes develop – Cranial-caudal (Head to tail) – Dorsal – ventral (Back to belly) – Left and Right (Left and Right) What happens during Gastrulation? B: Cells move through the primitive streak to create mesodermal and endodermal layers. Note the shape changes. • Primitive streak – Migration of epiblast cells also involves a transition of shape and type. – The migration of epiblast cells results in its differentiation into endoderm and mesoderm cell layer. – Epiblast cells that do not pass through the streak and remains on ‘top’ layer gives rise to the ectoderm layer. Formation of Notocord • A cellular rod of cells between the ectoderm and endoderm in the midline. • The primitive streak regresses and the notochord appears cranially from the primitive node. • Sometimes called the axial mesoderm due to location in midline within mesoderm layer. Dorsal view of the embryonic disc with a sagittal cross section. The primitive streak regresses caudally and notochordal process cranially from the primitive pit between the ectoderm and endoderm cell layers until it reaches the prechordal plate. Notocord What does the notochord do? • Acts as a support structure for the embryo. • Acts as a primary inducer to transform surrounding unspecialised embryonic cells into definitive tissue/organs. – Overlying ectoderm layer to thicken into neural plate. Early nerve system • Notocord develops along long axis • Region of Primitive node – Thickening of ectoderm – Neural plate • This folds into neural tube • Looking down on embryonic disc • Neural plate becomes nervous tissue • Notocord is NOT spine – Remnants are intervertebral discs • Clear development of – Front and back – Left right – Early mouth and anus Embryo development – in brief • Fertilisation, 2 daughter cells • 2, 4, 8, 16, all undifferentiated • 32 Cavity develops – blastula, Differentiation begins • Bilaminar disc – Epiblast – Hypoblast • Gastrulation – trilaminar disc – Endoderm – Mesoderm – Ectoderm https://youtu.be/ADlYn0ImTNg?t=4 Embryological Tissue Types Ectoderm Mesoderm Endoderm Epithelial Tissue Muscles Epithelial tissue Outer layer of skin Fibrous tissue (tendon etc) Glandular – lines gut Lining of hollow organs Bone & Cartilage Liver Skin glands, Hair, Claws Fat Nervous tissue Blood and lymph vessels Pharynx and respiratory tract (not nose) Salivary Glands Blood cells Mucous glands of nose and mouth Epithelium of bladder and urethra Organogenesis • From 3 weeks, rapid and increasingly complex organ development • Mostly complete by 8 weeks (human figures – most studied) • Moves from embryo to fetus • Stage is roughly similar relating to gestation length • Dog & cat – 63 days • Rabbit 28 – 35; Guinea Pig 59 – 72; Mouse 20; Most birds 21d hatching • The early stages especially until organogenesis is complete • Combination of cell growth, differentiation and apoptosis (eg webbing between fingers) Critical Further development • Heart – develops from mesoderm early • Tube-within-a-tube body plan – Series of folds – Fusion of fold • Gut – Foregut and Hind gut – Blind ending – Mid gut – connects to yolk-sac Failure of embryonic development • Failure to fertilise – ?5% in dogs • Embryonic death – Understand complexity of embryo development – Huge combination of gene expression and cell signalling – Small error – big consequence – Failure therefore not surprising – Can’t find dog data – but not uncommon – 25% in cattle by 28 days (33% in sheep) – Humans poss 62% lost by 12 days (maybe a third by 12 weeks) Failure of Pregnancy • Early development • Stage where most damage can occur – Chromosomal abnormalities – Teratogens (chemicals that harm embryo) – Infections • Placental creates physical barrier for fetus from around 9 weeks (human) – Blood-Placenta barrier – “None shall pass!” glucose, gas, amino acids only Relevance • Timing of damage is early, when cells are most vulnerable – why? • Helps investigations of: – Poor fertility in animals – Abortion storms in animals – Epidemiology • Schmallenberg Virus – Birth defects in cattle and sheep – Can work out when the infection happened • Distemper and Herpes virus in dogs (no pictures though) Common defects in practice • Umbilical hernia • Cleft palate – Both a failure of folding tissue to fuse • Atresia ani – No anus – often just below skin – Repair possible • Cardiac problems – Persistent right aortic arch – Ventricular or Atrial Septal Defects – Patent Ductus Arteriosus – All as a failure of foetal circulation to change to neonate Embryology • Fascinating but complex • Pockets develop that become the varied organs (as per the pre-learning videos) • Early organ development - 22 days for heart • Can detect heart on ultrasound of cattle at 30d • https://youtu.be/R93gu6OgENg (cool video, odd narration) • Important for understanding pregnancy (or egg) failure • Importance for cancer development • Cancers are essentially formed of the 3 basic embryological tissues – So surgery has to consider the layer on excision Stem Cells • Some cells are fully differentiated – “Dead end” no mitosis – WHY?? – Replaced from precursor cells – Derived from Stem cells • Usually occur in areas of rapid turnover – Skin – Gut – Blood • Stems cells, derive from endo ecto and mesoderm – Differentiate, – Remain as stem • Usually remain in resident tissue, few in number Applications of stem cells • Stem Cell transplants in humans – Treatment for varied diseases eg leukaemia – https://www.nhsbt.nhs.uk/what-we-do/transplantation-services/ste m-cells/ • Pluripotent cell induction – Eg ear cells – Can be induced to become stem cells with transcription factors (Wednesday session) • Preservation of endangered species – https://www.natures-safe.com/science – Potentially recover extinct species – Reduce genetic bottle-necks of small populations Bonus material • Organ Systems – Two areas where systematic organ systems approach is useful: • 1. Clinical Examination • 2. Post Mortem Examination – Why? • Systematic Approach – Why – Check everything/miss nothing through not looking – Creates a habit – Something to fall back on if cases are stressful/unexpected/unknown/need to play for time! Organ system examinations • Clinical Exam • Head to tail is usual • Comprehensive – Look, Feel, Listen, Smell – Pass on taste… • We will do a lot of this • Post Mortem • Systematic approach is critical • Every system is examined and reported – Vital if PME turns into a court case – Easy to overlook something Laminated tissue collection mats Cancer – when it goes wrong • Cells essentially no longer behave • Cells should – Divide when needed – Not divide when not needed – Live as long as needed – Be removed when not needed – Maintain specialised properties – Stay in proper place • A lot of the factors in cell division and function maintain this • A liver cell is a liver cell because it is in the liver. When cell division goes wrong • Cell Cycle regulation ensures errors are corrected • Apoptosis occurs if errors cannot be corrected • A single cell in error is usually not a problem – Usually removed • Problem arises if the fault is passed on in mitosis – And repeated • Tumour – proliferation of dividing cells • Benign – stays put eg lipoma – fat tumour, most dog mammary tumours • Malignant – spread – metastasise eg haemangiosarcoma. Drivers of cell faults • Cancer is essentially a genetic disease • Fault arises in the DNA of a cell • External factors – Radiation - melanoma in humans – Chemicals (smoking) – Viruses – Feline Leukaemia Virus, • Intrinsic factors – Error in DNA every 109 or 1010 nucleotide copies – Error 10-6 mutations per gene per cell division – 1016 Cell divisions per lifetime – Mutation on more than 109 occasions • Partly why cancers more common in older animals Cancer cells outcompete normal cells • Several factors involved in cancer cells establishing • Single cell not that big problem • Cancers cells – Reduced dependence on cell signals to control their survival etc – Can survive internal faults that normally leads to apoptosis – Can proliferate in culture indefinitely – Genetically unstable – increased mutation rate – Can survive in the wrong place (as they don’t need the signals) – Influence local environment to make it more hospitable for the tumour Embryology references • McGeady, T. A., et al. Veterinary Embryology, https://ebookcentral.proquest.com/lib/uclan-ebooks/detail.action? docID=1166590. • Larsen's Medial Embryology (bit more up to date) – https://librarysearch.uclan.ac.uk/permalink/44UOCL_INST/t99jj4/alma 991007473655903821 • Plus the videos in the prelearning • https://www.dnatube.com/video/2392/Embryonic-Origin-of-Tissues – Above, and many online sources show gastrulation to be an invagination of the embryo. It isn’t. It’s the formation of the trilaminar disc • https://embryology.med.unsw.edu.au/embryology/index.php/Carnegie _stage_5#Embryonic_Disc – Some nice images and animation (human embryology)