Developmental Biology The study of an organism from the time the egg is fertilized until birth During this time period the organism is called an embryo “The concept of an embryo is a staggering one, and forming an embryo is the hardest thing you will ever do. To become an embryo you had to build yourself from a single cell.” Scott Gilbert

From single cell to adult - a complex task

Developmental Biology has an extensive history, dating all the way back to Aristotle in 350B.C.! It is one of the fastest growing and most exciting fields in biology Developmental Bio is integrative - - –It incorporates molecular biology, physiology, cell biology, genetics, anatomy, cancer research, neurobiology, immunology, evolutionary biology, and ecology

Developmental Biology: Historical Perspective Aristotle: 1st Embryologist –Observed incubated chicks egg daily for the three weeks of development Two thousand years later (1600’s)... William Harvey, Marcello Malpighi take a closer look (microscopes are available) –Malpighi supports the a theory called preformation - all organs in are already present in the egg, but were miniature. This theory was believed true for many years.

Nicolas Hartsoeker depicts his theory that the entire human is already present in the head of the sperm

Developmental Biology: A Historical Perspective (cont.) The other school of thought felt that embryonic development occurred by “epigenesis.” This meant that all of the organs of the embryo were formed de novo (from scratch) at each generation Of course, modern biologists know that this is the case, but it was not until the ’s that this view gained favor *Remember that the cell theory didn’t arise until the 1800’s*

Edward Alton, 1917

Embryology from classical to modern From the 1800’s until just a few decades ago, embryology was limited to observing the embryo as it developed and manipulating the embryo to see what would happen –Cutting out pieces, rearranging sections, marking cells with dye to follow them along their path, culturing groups of cells away from the rest of the embryo

Although these studies may seem limited today, early embryologists were able to elucidate a wealth of information These early studies resulted in a set of major questions that became essential to understanding development

The questions of Developmental Biology The question of Differentiation –How does an egg cell give rise to 100’s of different cell types –Ex. Muscle cell, blood cell, neuron, fat cells, gametes

Differentiation into many cell types

The question of Morphogenesis –How do the cells in the embryo become organized into specific structures, like organs? –In other words, how do they take shape? –Organs also end up the the right places in our bodies, relative to each other and the overall body plan - how?

The question of Growth –During embryonic development, mitosis occurs at astoundingly fast rates –How do our cells know when to stop dividing? –How do cells on each side of our body divide at similar rates so that we are symmetrical?

The question of Reproduction –How do sperm and egg cells get set apart and given the instructions to make the next generation of organism? –What instructions are present in the nuclei and cytoplasm of the egg and sperm that give rise to the new organism?

The question of Evolution –Evolution involves inherited changes in developmental pathways –How do changes in development result in the creation of new body forms? Example: Organisms with wings vs. fins vs. legs

The question of Environmental integration –The environment of many organisms may effect their development Sometimes this is supposed to happen –The sex of many reptiles is determined by the temperature at which their eggs incubate Sometimes exposure to environmental conditions is detrimental –Exposure to chemicals during development can cause deformities –In humans this is observed when fetuses are exposed to chemicals from smoking, alcohol, drugs, and other teratogens

The Questions of Developmental Biology Differentiation Morphogenesis Growth Reproduction Evolution Environmental Integration

“Classical” Embryologists designed specific experiments to address the questions Observation Fate mapping Transplantation Cell defect experiments Isolation experiments Recombination experiments

Isolation experiment

Defect Experiment

Transplant Experiment

More recent advances in molecular biology, genetics and cell biology allow modern developmental biologists to revisit many of these “classical experiments” –Examine gene expression –Examine interactions of proteins –Examine how cells “talk” to each other –Explain why the results were obtained! We’ll examine these types of experiments during the semester

The Genetic Core of Development Before the discovery of DNA, and the modern understanding of genes, there was much debate about –heredity –how cells in the same organism could be different from each other In fact it was not until the 1920’s that embryology and genetics emerged as separate –Genetics: the transmission of traits to next generation –Embryology: the expression of those traits

The Genetic Core of Development The theory: genomic equivalence –Every cell in the embryo (and adult) has the same nuclear information (passed on from the fertilized egg through mitosis) The problem (in the eyes of an embryologist) –If the somatic nuclei in each cell have the same hereditary information, how can we end up with so many different cell types?? –WHAT DO YOU THINK?

The Proof We now know that the chromosomes in the nucleus contain all of our hereditary information, but how were embryologists convinced?

Cloning... Not as new as you might think! In 1952, Briggs and King replaced the nucleus of a fertilized egg with the nucleus of a cell from a frog blastula. The procedure was called Somatic Nuclear Transfer and is what we call “cloning”. The frog was identical to that of the donor embryo. INTERESTING POINT - transfers from later embryos - less successful

TOTIPOTENT Capable of directing the entire development of the organism!

The Genetic Core of Development Now that we know the nucleus contains all of the blueprints for development, we can design experiments that help identify genes and proteins involved in specific aspects of development.

Model Organisms - Why? Can be studied easily in a laboratory Have special properties that allow their mechanisms of development to be easily observed –Clear embryos, large cells, etc Can be easily manipulated - physically or genetically Have relatively fast development period Embryos can be readily obtained Genomes have been mapped

C. Elegans - Nematode worm

Sea Urchin pluteus larva

Zebrafish embryo

Mouse embryo

Human embryo