Developmental Biology (BIOL3530)

With Dr. Brian E. Staveley
Department of Biology
Memorial University of Newfoundland
History and Basic Concepts

Developmental Biology is at the core of all biology.

Developmental Biology is a fundamental aspect of biology.
It deals with complex mechanisms and many layers of "biological information" superimposed one on another.
It has the potential to be better and better understood in the very near future.
Recent advances in cell biology, genetics and molecular biology has and will continue to further our understanding of development unlike any time in the past.
Embryogenesis (embryo formation) determines the overall body plan.
Organogenesis (organ formation) determines subsections of the body (examples: vertebrate limb, Drosophila eye).
Often these processes share much more than is first obvious.
Many genes, proteins, signal transduction pathways and cell behaviours are common to both processes.

Model organisms in developmental biology
Although, we are mostly interested in human development (selfish reasons) many aspects of development are conserved in distantly related species.
The major Model organisms used to study the principles of development are...
nematode (Caenorhaditis elegans)
fruit fly (Drosophila melanogaster )
sea urchins
South African claw-toed FROG ( Xenopus laevis )
chick (Gallusgallus)
mouse (Mus musculis)
plant (Arabidosis thaliana)

Words to grow by
A/P axis:  anterior ~ head;  posterior ~ tail.
D/V axis:  dorsal ~ upper or back; ventral ~ lower or front.
P/D axis:  proximal ~ near; distal ~ far.
Lateral: to the side.
haploid ~ 1 set (of chromosomes) .
diploid ~ 2 sets (of chromosomes).

Major Developmental Biology Questions ...
1) What processes happen during development?
2) What mechanisms control development?
3) How can we control development?
4) To what goals can we apply controlled development?

Epigenesis versus preformation

Epigenesis (~upon formation) is a theory of development that states that new structures arise by progressing through a number of different stages.
Preformation theory suggests that all structures exist from the very beginning, they just get larger.
One preformation theory, the theory of the Homunculus suggested that a little human embryo was hidden in the head of every sperm.
[This theory has fallen out of favour.]
Since an embryo grows to be an adult and that adult produces another embryo and so on indefinitely, according to the theory of preformation, the very first embryo must included within itself tiny copies of all the future embryos (the Russian Doll Conundrum).

Cell theory

Organisms are composed of cells, the basic unit of life.
Both animals and plants are multicellular composites that arise from a single cell, therefore development must be epigenetic and not preformational since a single cell (the fertilized egg) results in many different types of cells.
Only the germ cells (egg and sperm) pass characteristics on to the offspring.
Somatic cells are not directly involved in passing on traits to the next generation and characteristics acquired during an animal's life are not passed onto the offspring.
Remember that "A hen is only an egg's way of making another egg." Samuel Butler

Meiosis and fertilization
Meiosis is the reduction division that allows diploid precursor cells to generate haploid germ cells.
At fertilization, a diploid is reformed by joining two haploid germ cells.
The diploid zygote contains equal numbers of chromosomes from each of two parents.
Observations of sea urchin eggs revealed that after fertilization the egg contains two nuclei which fuse to form a single nucleus.
The nucleus must then contain the "physical basis of heredity."
 

Xenopus Development (figure)

Early Xenopus development: fertilization
The unfertilized egg is a single large cell.
The animal pole, the upper part of the egg, has a pigmented surface.
The vegetal pole, lower region contains the yolk.
After fertilization, the male nucleus (from sperm) and female nucleus (from egg) fuse to form one nucleus.
After fertilization, cleavage begins without growth (mitotic division only).

Xenopus blastulation
After ~12 cycles of division make a layer of small cells surrounding a fluid-filled cavity (the blastocoel) that sits on top of the large yolk cells.
Three germ layers are mesoderm, endoderm and ectoderm
The mesoderm is located at the "equator" and becomes muscle, cartilage, bone, heart, blood, kidney
The endoderm is above the mesoderm and below the ectoderm and becomes gut, lungs and liver
The ectoderm sits above the endoderm and becomes the epidermis and nervous system
In the blastula, these layers are all on the surface and they interact!

Xenopus gastrulation & neuralation
Gastrulation is an extensive rearrangement of embryonic cells mesoderm and endoderm move to the inside of the embryo to give the basic body plan.
For the most part, the inside of the frog is now inside and the "outside" except for the skin is outside.
Notochord is a rod-like structure that runs from the head to the tail and lies beneath the nervous system.
Somites are segmented blocks of mesoderm form on either side of notochord which become muscles, spinal column and dermis (skin). Neuralation occurs when ectoderm above the notochord folds to form neural tube (becomes spinal cord & brain).
The tailbud stage follows the completion of neuralation.
 

Mosaic versus Regulative Modes of Development

Mosaic development
depends upon specific determinants in the one-celled zygote that are not divided equally between the daughter cells (asymmetric division).
Roux (1880's) destroyed one cell of a two-celled embryo (with a hot pin) to result in ~1/2 frog embryo.
Regulative development depends upon interactions between 'parts' of the developing embryo can result in causing different tissues to form (even if parts of the original embryo are removed).
Driesch destroyed one cell of a sea urchin embryo at the two cell stage and a normal appearing but smaller sea urchin larvae resulted.

Regulatory development: induction
Induction is a type of regulatory development.
This is a process where one tissue directs the development of another tissue.
A classical experiment:  Spemann & Mangold (1924)- graft of the blastopore lip of one newt onto another!
Note: The blastopore is the opening formed in early gastrulation through which cell migrate inside.
The Spemann Organizer can induce the formation of an ectopic axis (twinned embryo)

5 Processes of  Development
1. Cleavage Division:  No increase in cell mass
2. Pattern Formation:  A/P and D/V axes: Coordinate system
3. Morphogenesis:  take 3D form, neural crest migrates far. 1 egg- 250 types
4. Cell Differentiation:  cells become structurally and functionally different.
5. Growth:  cell multiplication, increase in cell size, deposit extracellular material (bone, shell) growth can be morphogenetic.

5 Cell Behaviours
Gene Expression- Cell Behaviour and Development. Gene activity gives cell identity.
1. Cell-cell communiaction
2. Cell shape changes
3. Cell movement
4. Cell proliferation
5. Cell death (apoptosis)

Inductive interaction
Inductive interaction is the process by which one group of cells change the fate of another group of cells.
The information to cause induction passes from cell to cell in the form of ...
1. secreted diffusible molecule
2. surface molecule receptor
3. gap junction (channel)
Competence: the state of being able to respond to inductive signals due to the presence of receptor or transcription factors.

Positional information directs pattern formation
Positional information directs pattern formation by giving positional values to cells.
The French Flag model (blue, white and red stripes) refers to the assignment of positional values in response to a morphogenic gradient.
This biological information must first be specified and
Then the value must then be interpreted .
Morphogen varies in concentration and directs different fates at different concentrations.

Source --------------> Sink
[high]                        [low]
Threshold concentrations: Different fates, different levels (ranges) of morphogen.

Cell fate
Cell Fate is what cells should become (not differentiation).
Specification cells keep their fate even when isolated and is tested by transplantation  (some cells change their fate).
Early embryonic cells are not narrowly determined, latter ones are!

DNA-------------------------------------->mRNA--------------------------------------->Protein
transcription & processing             nuclear export, translation & modification

Differential gene expression controls cell differentiation.
Common house-keeping genes do not cause cells to differ!
Developmentally specific transcription factors direct differential gene expression.

Development is progressive!
Lineage dependent fate: Cytoplasmic localization and asymmetric cell division control the fate of resulting cells.
Daughter cells become different & give different lineages.
Generative program: Development depends upon a progressive series of instructions.
An embryo needs to have each action to be built upon the previous action and that on the one before.
Development instructions are not a "blue print" but is a structural list of actions.
Lateral Inhibition:  Many structures are regularly spaced.
Cells that form a structure stop neighbouring cells from doing the same (feathers, compound eye faucets).

email me at bestave@mun.ca