Early human development 2024 (1).pdf

Early Human Development Dr. Hilary Sheppard Development is Amazing Second Law of Thermodynamics entropy will increase over time Foetal Development 1-4 weeks 35-38 weeks Table 29.2 – Tortora, 2019 Learning Objectives Describe the major developmental events in week 1 Fertilisation Cleavage of the zygo...

Early Human Development Dr. Hilary Sheppard Development is Amazing Second Law of Thermodynamics entropy will increase over time Foetal Development 1-4 weeks 35-38 weeks Table 29.2 – Tortora, 2019 Learning Objectives Describe the major developmental events in week 1 Fertilisation Cleavage of the zygote Formation of the morula and blastocyst Implantation Describe some of the developmental events in weeks 2 - 4 Trophoblast development and embryonic disk Gastrulation Structures derived from the three primary germ layers Understand what stem cells are and why we need them List the hierarchy of stem cells Describe one clinical application of stem cells What does embryogenesis achieve? Patterning – cells acquire identity in space and time The major axis are defined – anterior/posterior dorsal/ventral Three germ layers are defined Rudiments of the major organs Gastrulation generates three germ layers Ecto - outside Meso - between Endo - inside Fertilisation Sperm enters oocyte Meiosis II is completed Fig 29. 1– Tortora, 2019 Cleavage and Formation of the Blastocyst Fig 29. 2– Tortora, 2019 Implantation Fig 29. 5– Tortora, 2019 Development of the trophoblast Syncytiotrophoblast Chorionic villi – fetal placenta Cytotrophoblast Uterine endometrium Fig 29.6a and Fig 29.11– Tortora, 2019 Development of the bilaminar embryonic disc Hypoblast Epiblast Uterine endometrium Fig 29.6a – Tortora, 2019 Gastrulation "It is not birth, marriage, or death, but gastrulation which is truly the most important time in your life." Prof. Lewis Wolpert Photo from https://alchetron.com/Lewis-Wolpert Gastrulation Embryonic disc Connecting stalk Amnion Yolk sac Formation of the primitive streak Primitive streak Ectoderm Mesoderm Endoderm Fig 29.7 – Tortora, 2019 Embryonic folding Fig 29.12 – Tortora, 2019 https://www.youtube.com/watch?v=EaktR9Sp0mE https://www.hhmi.org/biointeractive/h uman-embryonic-development Human embryonic development It is AMAZING! Foetal Development 1-4 weeks 35-38 weeks Table 29.2 – Tortora, 2019 Differentiated cells have limited divisions Stem cells replace themselves and can generate differentiated daughter cells We need stem cells for Growth Renewal Repair Decreasing developmental potential A stem cell is defined as a cells that divide to form one daughter that goes on to differentiate, and one daughter that retains its stem-cell properties Differentiation The Stem Cell Hierarchy Nature Reviews Genetics. 19, 595–614 (2018). Fig. 1 https://doi.org/10.1038/s41576-018-0040-z Stem cells in the skin Unipotent stem cells in the skin allow for constant renewal 6 Wolpert et al 5th ed. Fig 8.20 and 8.21 Stem cells in the skin 19 Cytokeratin 14 10 Figure courtesy of Dr. Vaughan Feisst, University ofAuckland Overview of our ex vivo gene therapy strategy Aim is ~5% epidermal stem cell retention (De Luca et al., 2013) Image created using BioRender by Alex du Rand, Sheppard lab (2023) Edited skin expresses Col7 and stem cell markers DAPI Collagen 7 FOX-M1 EB donor cells Edited EB cells 6% Co-expression Healthy control Alex du Rand - Sheppard laboratory (2023) Let’s recap How does it all start? With fertilisation, n + n = 2n What happens next? Cleavage What happens after cleavage? Blastula formation/implantation How do we create three germ layers? Gastrulation Ecotderm – skin, mesoderm – connective tissues, endoderm - gut What happens after gastrulation? Organogenesis Why do we need stem cells? To replace differentiated cells Growth, repair, renewal Clinical utility of stem cells? Long lasting skin grafts (gene edited) Any questions? Piazza Want to learn more? BIOSCI201 BIOSCI356