Developmental Biology - M33771 Module Notes

Introduction to Development, Stem Cells, and Differentiation

Module Overview

  • Instructors:
    • Susanne Dietrich (SMPBS), Module Coordinator
    • Frank Schubert (SELS)
    • Jordi Cayuso (SMPBS)
    • Ryohei Sekido (SMPBS)

Development: A Progressive Process

  • Development is a process of progressive change in an organism.
  • Stages:
    • Fertilized egg (zygote)
    • Embryonic development
    • Newborn
    • Postnatal development
    • Adult
    • Regeneration
    • Aging
  • Fields of Study:
    • Embryology
    • Developmental Biology

Module Aims

  • Develop a basic understanding of prenatal development and regeneration.
  • Explore the implications of developmental biology research for science and society.
  • Instill an appreciation for multidisciplinary approaches in studying development.
  • Develop fundamental laboratory and observation skills for research in developmental biology.
  • Develop language and communication skills for developmental biology.
  • Provide foundations for the 3rd year module M33321 “Mechanisms of Development,” which explores cellular, molecular, and genetic control of developmental processes, BSc, and MRes projects.
  • Step up from year 1; this is a research-informed module that goes beyond textbooks.

Module Outcomes

  • Describe phases of vertebrate/human development from fertilization to organogenesis.
  • Discuss epigenesis and the contribution of cell proliferation, patterning, and differentiation to embryonic development.
  • Describe embryonic induction and the role of morphogens.
  • Discuss similarities and differences in vertebrate development and the use of model organisms.
  • Describe experimental strategies in developmental biological research.
  • Discuss how birth defects result from aberrant development.
  • Discuss the significance of stem cells in tissue regeneration and therapy.
  • Apply basic laboratory skills in tissue preparation, observation, and description.
  • More than year 1: discuss = building scientific arguments based on experimental data.

Background Knowledge

  • Animal Phylogeny: Evolutionary relationships of animals
    • Protostomes vs. deuterostomes
    • Invertebrate chordates vs. jawless and jawed vertebrates
    • Cartilaginous vs. bony vertebrates
    • Ray-finned vs. lobe-finned/limbed vertebrates (incl. tetrapods)
    • Amniotes (mammals, birds, reptiles)
  • Gene Regulatory Networks
    • Gene, gene promoter, and enhancer
    • Transcription (mRNA production) vs. translation (protein production)
    • Transcription factors and their function
    • Signaling molecules in cell-to-cell communication
  • Human genetic diseases
  • Environmental factors, endocrine disruptors

Module Delivery

  • Lectures and workshops covering:
    • Developmental Anatomy
    • Fertilization and IVF
    • Cell division, patterning, and cell differentiation
    • Gastrulation and the significance of germ layers
    • Organogenesis:
      • Nervous system
      • Head and face
      • Endoderm and its derivatives (gut, lungs, pancreas, liver)
      • Muscle
      • Heart
      • Skeleton
      • Urogenital/reproductive system
      • Vasculature and blood
    • Birth defects
    • Embryonic and adult stem cells, tissue regeneration
    • Experimental approaches in developmental biology
  • Practical sessions: Microdissection and microscopic observation
  • Detailed timetable and practical & workshop handouts on Moodle

Timetable Highlights (M33771, 2024/25, TB2)

  • Week 26:
    • Lecture 1: Introduction (Developmental Biology, Module Structure, Key Events, Assessments) - SD
    • Workshop 1: Developmental Anatomy (Key Structures, Changes Over Time) - SD, JC, RS, FS
  • Week 27:
    • Lecture 2: Fertilisation, the first cell divisions, embryonic stem cells and germ cells, IVF - SD
    • Lecture 3: Gastrulation and the generation of the three germ layers endoderm, mesoderm and ectoderm - SD
  • Week 28:
    • Lecture 4: Endoderm development, and how it makes the gut, lungs, pancreas and liver - JC
    • Workshop 2: Paint, cut and paste - experimental approaches in developmental biology - SD, JC, RS, FS
    • Lecture 5: Ectoderm development, making the sense organs and the nervous system (1) - neural induction, neurulation, neural crest cells, placodes, carly patterning - FS
  • Week 29:
    • Lecture 6: Ectoderm development, making the sense organs and the nervous system (2) - neuronal differentiation & migration, axonal pathfinding - FS
    • Lecture 7: Segmented structures 1: body parts from Lego blocks -trunk paraxial mesoderm segmentation and the formation of muscle and vertebrae and ribs - SD
    • Lecture 8: Segmented structures 2: pharyngeal arches and the building of head and face, ectomesenchymal neural crest cells - SD
    • Seminar: Q/A1 for L1-8 and workshops 1-2 - SD, FS, JC
  • Week 30:
    • Seminar: Q/A2 for L9 and workshops 3 - SD
    • Lecture 9: Blood and - FS
    • Workshop 3: Model organisms - SD, FS, JC, RS
  • Week 33:
    • Assessed practical: Observing and recognising developmental anatomy & practical skill development: microscopy, microdissection
      • 2 annotated anatomical drawings, counts 15% towards the final module mark
  • Week 34:
    • Lecture 12: Development of the urogenital and reproductive system from the intermediate mesoderm - SD
    • Lecture 10: Development of the heart and great vessels -SD
  • Week 35:
    • Lecture 11: Limb development from the somatic lateral mesoderm - SD
    • Lecture 13: Tissue/organ regeneration and stem cells in development and therapy - SD
    • Seminar: Q/A3 for L10-13 (or L9-13) - SD, FS, RS
  • Week 39:
    • Assessed Group presentations,Experimental approaches and model organisms suitable to investigate a self-chosen problem in developmental biology. Counts 35% towards the final module mark. NOTE: peer-moderation - SD, FS, JRS
    • Workshop 4: Embryonic induction and morphogens - SD, JR5, JC, RS, FS
  • Week 40:
    • Seminar/ Revision Workshop R1: Revisions/exam prep: content of the module - SD FS JC RS
    • Choice: Lab demo -1, SD Research on precursor/ stem cells in cardiovascular and musculoskeletal development - SD lab
    • Choice: Lab demo -2 F$ Research in developmental neurobiology - chicken model - FS lab
    • Choice: Lab demo -3 JC Research in developmental neurobiology - zebrafish model - JC lab
    • Choice: Lab demo -4 R$ Research in gender-specific disease and stem cell/ organoid models for germ cell production - R$ lab
    • Choice: Lab demo -5 M Research of the European Xenopus Resource Centre = the 'frog centre'
    • Seminar/ Revision Workshop RZ: Revisions: data analysis - SD
  • Week 42:
    • Summer exam period
      • 1.5 h exam planned
      • exam for Mon 20/5/2024 noon-1:30pm
      • MCQ testing knowledge, understanding and higher cognitive skills incl. data analyses. Counts 50% towards the final module mark.

Assessment Structure

  • Item 1: Annotated anatomical drawings (15%)
    • Week 33
    • Replacement: Essay on developmental anatomy and ethics of animal research
  • Item 2: Group presentation (35%)
    • Week 39
    • Replacement: Essay on the group's chosen topic
  • Item 3: Exam (50%)
    • Summer exam period
    • Replacement: Viva testing knowledge and understanding

Presentation Guidelines

  • Groups of 5-6 students.
  • Sign-up sheet available.
  • The whole group must know the "whole story".
  • Use the consolidation week to prepare and practice.

Practical Information

  • Inform instructors if you cannot participate in the practical.

Resources

  • Moodle module ‘Development’
  • Textbooks
    • Slack, J.M.W. Essential Developmental Biology. Wiley-Blackwell
    • Gilbert S.F. Developmental Biology Sinauer, Sinauer Associates Inc.
    • Wolpert L. and Tickle C., Principles of Development, Oxford University Press
    • Schoenwolf G. et al., Larsen’s Human Embryology, Churchill Livingstone
  • Academic websites
    • Virtual embryo (http://www.ucalgary.ca/UofC/eduweb/virtualembryo/ )
    • Zygote (http://zygote.swarthmore.edu/ )
    • Developmental mechanisms (http://www.biology.arizona.edu/developmentalbio/problemsets/DevelopmentalMech anisms/developmentalmechanisms.html )
    • Embryo images (http://www.med.unc.edu/embryo_images/ )
  • Suggestions for extra reading in the lectures and on Moodle

Workshop 1 Preparation

  • Download and have pictures of young embryos in the 1st 1/3 of development available
  • Find images of chicken embryos at 36 hours and 4 days of development (= stages for the practical)
  • Look at the “word clouds” and find out about what these words mean
  • Start building a glossary of scientific terms

Key Concepts (Word Clouds)

  • Gastrulation, germ layers, primitive streak/blastopore, Hensen’s node/dorsal blastopore lip/Mangold-Spemann organiser, rostral-caudal, dorsal-ventral, left-right, tail bud, notochord.
  • Nervous system development, neural plate, neural tube, neurulation, brain vesicles: telencephalon, diencephalon, mesencephalon, rhombencephalon, head-trunk border, spinal cord, floor plate & roof plate of the neural tube.
  • Neural crest cells, neuroglial neural crest cells, ectomesenchymal/skeletogenic neural crest cells, skull bones, jaws.
  • Sense organ development, placodes, sensory placodes/vesicles, optic vesicle, otic (acoustic) vesicle, nasal (olfactory) vesicle.
  • Gastrointestinal development, endoderm, foregut, stomach, liver, pancreas, lung, mouth, anus.
  • Foregut-pharynx, Pharyngeal = branchial arches, filter feeding, respiration - gills, jaws and active predation, gnathostomes (jawed vertebrate), agnathans (jawless vertebrates).
  • Muscle and vertebral column, segmented paraxial mesoderm, somites, myotome - muscle, sclerotome - vertebral column and ribs, dermomyotome – precursor of myotome and dorsal dermis.
  • Urogenital development, intermediate mesoderm, nephric duct, nephric tubules, gonad development, germ cells.
  • Heart development, cranial lateral mesoderm, 1st and 2nd heart fields, heart tube, heart looping, atrium, ventricle, in- and outflow.
  • Blood and vascular development, vasculogenesis, angiogenesis, angioblasts, blood islands, dorsal aorta.
  • Paired fins, paired limbs, Limb bud, apical ectodermal ridge, hand (foot) plate, digits, actinopterygian (ray-finned vertebrate), sarcopterygian (lobe-finned/limbed) vertebrate.

Core Questions of Developmental Biology

  • What questions does Developmental Biology address?
  • Why does Developmental Biology integrate so many biological/biomedical disciplines?

Fundamental Principle

  • "Omne vivum ex ovo" - 'all life from the egg'
  • All animals develop from a single cell, the fertilized egg.

Evolution of Multicellularity

  • Sexual reproduction and embryonic development evolved multiple times.

Epigenesis vs. Preformation

  • Epigenesis: (Aristotle, 4th century BC)
    • Development from simple to complex.
    • De novo emergence of new structures.
  • Preformation: (17th-19th century)
    • Simple unfolding of a preformed structure.
    • Structure present in egg or sperm.
  • Epigenesis prevails through careful observation of developing embryos documenting gradual formation of new morphological features during embryogenesis.

Model Organisms

  • Pluteus larva
  • Xenopus laevis (vertebrate, amphibian)
  • Zebrafish (vertebrate, fish)
  • Caenorhabditis elegans (C. elegans, nematode = roundworm)
  • Chicken (vertebrate, bird)

Key Questions in Developmental Biology

  • Cell differentiation: How does a zygote give rise to hundreds of different cell types?
  • Morphogenesis: How does a zygote acquire organized form, resulting in distinct tissues and organs?
  • Growth control and coordination of cell division: How is growth regulated and coordinated with cell division?
  • Reproduction: How do egg and sperm combine to form a zygote and a multicellular organism?
  • Evolution: How do changes in development lead to new body forms?
  • Environmental integration: How does the environment influence development (e.g., sex determination in crocodiles)?

Tools for Studying Development

  • Fate Maps: Diagrams showing the developmental fate of particular regions in the embryo.
  • Clonal Analysis: Tracing a single cell and its descendants to determine their fates; identifies allocation territories.
  • Gross Anatomy: Observing normal stages of development.

Gene Expression Patterns

  • In Situ Hybridization (ISH):
    • Detects a gene's mRNA.
    • Blue staining indicates cells where the gene is expressed (active).
    • Housekeeping genes are expressed everywhere, but specific genes have specific expression patterns.
    • Genes with specific expression patterns can be developmental markers or developmental control genes.
    • Expression of developmental control genes is tightly regulated.

Experimental Approaches

  • Goal: Understand gene function and gene regulatory networks.
  • Gain-of-Function Experiments:
    • Example: Antp gene in Drosophila
      • Normally expressed in the thorax.
      • When wrongly expressed in the head, antennae are transformed into legs.

Tools and Methods Summary

  • Describe, Detect, Reveal:
    • Change of form (morphogenesis)
    • Trace cells
    • Gene expression patterns
    • Activity of gene regulatory elements (promoters, enhancers, silencers)
  • Manipulate:
    • Gene function (loss of function, gain of function)

Module Summary

  • Technical aspects of the module.
  • Module content overview.
  • The module is informed by ongoing research.
  • Flavour of how we lectures will deliver content