Developmental Biology Lecture Notes

Introduction

• Neil Vargsson, a developmental biologist from Forrester Hill, will discuss how a single cell develops into a fully formed organism.
• The lecture aims to explain the process of development, focusing on the formation of body structures like limbs.
• Research focuses on limb development, including the number of fingers and the equal length of arms and legs, despite the lack of direct communication during development.

From Egg to Organism

• Fertilization initiates the process, creating a zygote with DNA from both parents.
• Gastrulation is a key process in embryo formation, leading to the creation of germ layers.
• Germ layers differentiate into various structures: nervous system, somites, and internal organs through organogenesis.
• Development is a complex process with multiple events occurring simultaneously.

Principles of Vertebrate Development

• Vertebrate development follows five basic principles:
  • Cleavage (Cell Division): The zygote divides into smaller cells without increasing in size.
  • Morphogenesis: Includes gastrulation and neurulation, which establish the embryo's structure.
  • Regional Specification (Pattern Information): Cells are assigned specific fates, determining their differentiation.
  • Cell Differentiation: Cells specialize into 200 different types in the vertebrate body.
  • Growth: Increase in size.
• Development is genetically controlled.

Cleavage

• Cleavage patterns vary among species (radial, holoblastic, meroblastic, superficial, spiral).
• Holoblastic: Complete cleavage.
• Meroblastic: Incomplete cleavage, common in chicks and zebrafish with yolk sacs. Cell division occurs on top of the yolk sac before gastrulation.
• In humans, the zygote undergoes several divisions to form a morula (ball of cells) without an increase in size.
• At the morula stage, cells release fluid to form the blastocyst with an inner cell mass.
• The inner cell mass gives rise to the embryo proper, while surrounding cells form the yolk sac. This process takes about ten days in humans.
• Fluid release from the inner cell mass leads to the formation of the epiblast and hypoblast.
  • Hypoblast: becomes the Yolk sac.
  • Epiblast: will make every single cell in one's body.
• The embryo is initially flat before developing into a three-dimensional structure.

Gastrulation

• Gastrulation is a critical stage in development; failure leads to embryo death.
• Lewis Walpert: Gastrulation is the single most important event in one's life.
• In humans, gastrulation begins around day 15 or 16 on the epiblast.
• A primitive streak forms with a node (organizer) at its tip.
• The primitive streak moves from the posterior to the anterior part of the embryo, inducing cell proliferation and migration.
• Cells migrate into the primitive streak and underneath the epiblast to form the endoderm and mesoderm.
• As the primitive streak progresses, the embryo enlarges and becomes shield-like.
• Prenotochordal cells contribute to the formation of the nervous system.
• The epiblast becomes the ectoderm, while the mesoderm and endoderm form from the migrating cells.

Germ Layers

• The three germ layers differentiate into specific tissues and organs:
  • Ectoderm: Forms the skin and nervous system.
  • Endoderm: Forms the internal organs.
  • Mesoderm: Forms limbs, skeleton, muscle, heart, and blood.
• In vertebrates, the endoderm is in the middle (yellow), and the ectoderm is on the outside (blue).

Neurulation

• Neurulation begins as gastrulation occurs, forming the brain and neural tube.
• The ectoderm is induced to become neural ectoderm by signals (BMPs and Wnts) from prenotochordal cells.
• The neural ectoderm proliferates to form the neural plate, which folds to create the neural tube.
• Failure of neurulation results in spina bifida.
• The neural tube closes, and the skin covers it through a wound-healing process.

Neural Crest Cells

• Neural crest cells, located on the neural folds, migrate away after neural tube closure.
• Neural crest cells form the skull, teeth, nerves in the head, and part of the heart's outflow tract.

Somite Formation

• Somites support the neural tube and form the vertebral column.
• Somites produce:
  • Vertebral column.
  • Muscle.
  • Skin.
• The first somite appears around day 20, with 35 somites forming by day 30, corresponding to 35 vertebrae.

Summary of Early Development

• Day 19: Neurulation and gastrulation occur simultaneously.
• The head forms first to allow maximum brain development (200 billion cells).
• Day 20: Somites form alongside the neural tube.
• Day 22: The neural tube closes, but the head and posterior remain open.
• Day 23: The majority of the neural tube is closed, with somites forming. The heart and ears also begin to form.

Embryo Folding

• The flat embryo needs to become a cylinder with the endoderm in the middle.
• The edges of the embryo become heavier and fold downward.
• The ectoderm folds and meets in the midline, chopping off the yolk sac.
• This process creates a three-dimensional cylinder with the endoderm in the middle and the ectoderm on the outside.
• By day 28, the embryo is fully enclosed, with the gut forming in the middle and a cavity created by the cutoff yolk sac.
• The yolk sac is cut off due to the formation of the placental connection around three weeks.

Formation of the Embryo

• By day 28, the embryo has eyes, ears (otic placode), pharyngeal arches, and a beating heart.
• Limbs start to form, and the body is almost completely closed, except for the umbilical cord area.
• After eight weeks, the embryo is fully formed and becomes a fetus.

Phylotypic Stage

• Vertebrate embryos share similar developmental mechanisms.
• There is a phylotypic stage where embryos (xenopus, chick, mouse, zebrafish) look alike.
• Species-specific differences emerge after the phylotypic stage.
• Chickens, fish and mice are heavily studied in particular to study development since the phylotypic stage utilizes similar process across species ensuring similar structures.

Genetic Control

• Development is genetically controlled by genes such as HOX genes.
• HOX genes:
  • Master control genes (transcription factors).
  • Establish the anterior-posterior axis.
  • Control vertebrae differences and brain divisions.
  • Pattern limbs and determine finger identity.
  • Regulated by retinoic acid (vitamin A derivative).
• PAC-six:
  • Example of a homeobox gene that makes eyes in flies, mice, and humans.
  • Variations (mutations) in PAC-six lead to eye defects or blindness.

HOX Genes and Segmentation

• HOX genes control cell fate and regional identity, extensively studied in flies.
• HOX genes control segment development; altering their position changes the fly's structure (e.g., legs growing where antennae should be).
• Mammals have four sets of HOX genes due to duplications, reflecting greater complexity.
• HOX genes set up a HOX code that determines cell fate and differentiation.

Early Embryo Picture

• Fertilized oocyte with sperm entry.
• Cleavage and gastrulation lead to the formation of three germ layers.
• The epiblast is transformed into the embryo.

Video Examples

• Zebrafish Embryo:
  • Egg cells cleave and undergo gastrulation and organogenesis.
  • Cells migrate to form germ layers, and the head, eyes, and somites develop.
• Xenopus Embryo:
  • Cleavage leads to a ball of cells that gastrulates.
  • Head forms, and the embryo develops into a tadpole.

Chicken Embryo

• Chicken embryos are used to study limb development without a microscope.
• Chicken limbs develop similarly to human limbs.

Normal vs. Abnormal Development

• Normal Development:
  • Single cell ⟶ Fully formed embryo.
  • Gastrulation.
  • Neurulation.
  • Somatogenesis.
  • Embryo folding.
• Three percent of all human births have a birth difference due to errors in these processes.
• The fact that ninety-seven percent of all babies do not have a birth difference is something of a marvel.