The Muse: the embryo

Developmental Biology

Major Questions

• Growth: regulation of size • Morphogenesis: generation of ordered form • Differentiation: generation of cellular diversity • Reproduction: why and how is the germ line so special • Evolution: how do changes in development create new body forms • Environmental integration: how does the environment influence development

Approaches

• Anatomical : Comparative and Evolutionary Embryology, Teratology, Modeling • Experimental • Genetic

The Anatomical approach Anatomical approach : descriptive, based on the observation of morphological changes Discovery of primary germ layers, inductive interactions amongst them.

Comparative embryology • Aristotle in 350 B.C noticed that: 1) Animals are born in different ways: - oviparity: from eggs body - viviparity: live birth - ovoviviparity: producing a egg that hatches inside the 2) Two major cell division patterns by which embryos are formed: - holoblastic pattern of cleavage: the entire egg is divided into smaller cells - meroblastic pattern of cleavage: only part of the egg is destined to become the embryo.

Epigenesis and preformation • In 1672, Marcello Malpighi published the first microscopic account of chick development.

• Debate: epigenesis X preformation - Epigenesis: organs of the embryo are formed from scratch - Preformation: organs of the embryo are already present in miniature form • In 1767, Kaspar Wolff proclaimed that he believed in the truth of epigenesis after working with chick embryos and seeing the heart and blood vessels to develop. • The end of preformationism did not come until 1820s with Christian Pander, Karl Ernst von Baer, and Heinrich Rathke.

Christian Pander- 1820s • Pander studied the chicken embryo and discovered the germ layers: - Ectoderm: generates the outer layer of the embryo. It produces the surface area (epidermis) of the skin abd forms of the brain and nervous system.

- Mesoderm: generates the blood, heart, kidney, gonads, bones, muscles and connective tissue.

- Endoderm: innermost layer of the embryo and produces the epithelium of the digestive tubes and its associated organs (including the lungs).

• Triploblastic- animals with 3 germ layers • Diploblastic- animals with 2 germ layers

1.4 The notochord in the chick embryo Karl Ernst von Baer discovered the notochord and the mammalian egg.

Comparative / Evolutionary Embryology Von Baer rules: vertebrate embryos are very similar, sharing various structures. As they develop, they diverge. (pages 9 and 10) Darwin: community of embryonic structure reveals community of embryonic descent; comparison of embryonic forms help in establishing evolutionary relationships

1.6 Fate maps the early gastrula stage • Cell lineage: following individual cells to see what they become.

• Techniques to follow normal development: FATE MAPPING (vital dye marking, radioactive or fluorescent labeling, genetic marking).

1.7 Fate map of the tunicate embryo – Edwin Conklin, 1905

1.8 Vital dye staining of amphibian embryos

1.9 Fate mapping using a fluorescent dye- zebrafish (Part 1)

1.9 Fate mapping using a fluorescent dye- zebrafish (Part 2)

1.10 Genetic markers as cell lineage tracers Chimeric embryos: graft of quail cells inside of a chicken embryo. Also called “mosaic” embryos.

The Cellular Basis of Morphogenesis • Cells are constantly changing during embryogenesis • Morphogenesis is brought about through a limited repertoire of variations in cellular processes within these two types of arrangements: - Direction and number of cell divisions - Cell shape changes - Cell movement - Cell growth - Cell death - Changes in the composition of the cell membrane or secreted products • Cell migration: one of the most important contributions of fate maps has been their demonstration of extensive cell migration during development.

1.11 Neural crest cell migration (A) Mary Rawles (1940) showed that melanocytes of the chicken originate in the neural crest (NC).

(B)(C) Weston (1963) demonstrated that migrating NC cells gave rise to melanocytes, and peripheral neurons.

Medical Embryology • Between 2 and 5% of live births show observable anatomical abnormalities.

• In the lack of experimental data…birth defects help us understand normal human development.

• Some birth defects are produced by mutant genes or chromosomal abnormalities, while others are produced by environmental factors.

• Genetic defects: malformations – often appear as syndromes Use of animal models to identify genetic, cellular and molecular basis of human syndromes.

Ex: kit mutation leading to piebaldism • Environmental defects: disruptions Responsible agents: teratogens – chemicals, viruses, radiation Ex: thalidomide leadind to phocomelia

1.15 Developmental anomalies caused by genetic mutation • Piebaldism- dominant mutation on gene Kit. Includes anemia, sterility, unpigmented regions of the skin and hair, deafness, and absence of nerves that cause peristalsis in the gut.

1.16 Developmental anomalies - environmental agent (Part 1) • Disruptions: abnormalities caused by exogenous agents (certain chemicals or viruses, radiation, or hyperthermia).

• The agents responsible for these disruptions are called teratogens.

1960s: increase of a previous rare syndrome of congenital abnormalities. Phocomelia caused by the drug thalidomide which were prescribed to pregnant women as a mild sedative.

1.16 Developmental anomalies - environmental agent (Part 2)

Mathematical Modeling • Base development on formal mathematical and physical principles.

• Mathematical modeling is strong in pattern formation and growth.

• Growth - Isometric: all components grow at the same rate, uniform (mollusk shells) body) - Allometric: components grow at different rates (human • Patterning - Turing: reaction-diffusion model (tooth development)

1.17 Equiangular spiral growth patterns

1.18 Allometry in humans

1.20 Reaction-diffusion (Turing model)

1.21 Photograph of the snail

Oliva porphyria

(L), and a computer model

1.22 Mammalian tooth cusp pattern modeled by reaction-diffusion equations

1.22 Mammalian tooth cusp pattern modeled by reaction-diffusion equations