What is development?

Process in which a single cell (zygote) cleaves and grows into a multicellular organism with: - an organized body plan - differentiated cell, tissues, and organs
The science of becoming

1 cell

Questions of Developmental Biology

Differentiation - How can the fertilized egg generate so many different types of cells? Morphogenesis - How can these cells form specific 3-D structures such as tissues and organs in the correct location? Growth - How is cell division so tightly regulated? Reproduction - How are germ cells set apart to form the next generation? Evolution - How do changes in development create new body forms and how does this relate to evolution? Environmental integration - How is the development influenced by cues from the environment?

A little bit o developmental biology history

Aristotle William Harvey Malpighi Epigenesis vs. preformation debate Discovery of the germ layers

Figure 1.1 Some Representative Differentiated Cell Types of the Vertebrate Body

The derivation of organs is constant in all organisms

Figure 2.1 Developmental History of the Leopard Frog, Rana pipiens

In the 19th century, embryology was tool used to better understand evolution (establishing phylogenetic relationships).
Haekel and others - early developmental stages were essentially the same.

Unform

Karl Ernst von Baer Four generalizations about vertebrate development

- The general aspects of a large group of animals appear earlier in embryonic development than do the more specialized ones.
- Less general characters develop from more general ones. -The embryos of a particular species diverge more and more from those of other animals as development proceeds. -The young embryo of a "higher" animal is not like the adult of a "lower" one, but instead resembles its early embryo.

Differentiation - the development of specialized cell types.

Commitment and Cell Fate

Differentiation is preceded by commitment of a cell to a certain fate.

Commitment - 2 stages
1. Specification - cells are capable of differentiating autonomously when placed in a neutral environment. 2. Determination - cells are capable of differentiating autonomously even when placed in another region of an embryo.

Determination can occur as a result of: 1. Segregation of cytoplasmic determinants Sometimes called morphogenetic determinants.

2. Cell - cell interactions Induction - a cell - cell interaction that affects cell fate -Diffusible factors -Cell bound molecules -Extracellular matrix

Morphogen Gradients
Cell fates can be specified by specific amounts of soluble molecules secreted from a distance from the target cells.

Soluble molecule known as a morphogen If morphogen specifies different fates at different concentrations - morphogen gradient.
Source Sink

Figure 3.19 Activin (Or a Closely Related Protein) Is Thought to Be Responsible for Converting Animal Hemisphere Cells into Mesoderm

Figure 3.20(1) A Gradient of Activin Causes Different Gene Expression in Xenopus Animal Cap Cells

Figure 3.20(2) A Gradient of Activin Causes Different Gene Expression in Xenopus Animal Cap Cells

Figure 3.22(1) The Stem Cell Concept

Stem cells - have the capacity to divide indefinitely and can give rise to more specified cells.

Figure 3.21(2) The Stem Cell Concept

Morphogenesis and Adhesion

How can these differentiating cells organize themselves to create complex structures (i.e. organs)?

How do the organs form in particular locations and how do migrating cells reach their location?

Figure 3.23 Reaggregation of Cells From Amphibian Neurulae Townes and Holtfreter, 1955

Differential Cell Affinity

Cells from different tissues display selective affinities maintains spatial order

Figure 3.24(1)

Final positions of reaggregated cells reflect their embryonic positions

Figure 3.24(2) Sorting Out and Reconstruction of Spatial Relationships in Aggregates of Embryonic Amphibian Cells (After Townes and Holtfreter 1955.)

Townes and Holtfreter experiments: 1. Reaggregated cells become spatially segregated. 2. Final positions of reaggregated cells reflect their embryonic position. 3. Tissues display selective affinities. 4. Selective affinities change during development.

Figure 3.25 Reconstruction of Skin From a Suspension of Skin Cells From a 15-Day Embryonic Mouse

Figure 3.26 Aggregates Formed by Mixing 7-Day Chick Embryo Neural Retina Cells with Pigmented Retina Cells

Differential Adhesion Hypothesis

Tissues form hierarchies of adhesiveness
A A > A B or B B A A < A B

?
B B

?
A A

>>>>>>> A

Figure 3.27 Hierarchy of Cell Sorting in Order of Decreasing Surface Tensions (or Surface Cohesions)

What is the molecular basis for cell-cell adhesion?

adherins junction

Several major cadherin classes in vertebrates:

E-cadherin (epithelial) P-cadherin (placental) N-cadherin (neural) EP-cadherin R-cadherin (retina) B-cadherin Protocadherins Cadherins join cells together by binding to the same type of cadherin on another cell - homophilic binding Cells regulate: the type of cadherin the amount of cadherin timing

Figure 3.29 Cadherins Are Important for Maintaining Cohesion Between Developing Cells

Antisense oligo against a maternal cadherin mRNA

Figure 3.30 The Importance of N-Cadherin in the Separation of Neural and Epidermal Ectoderm

Dom Neg N-cadherin injected into left side of 4-cell embryo

Other Factors in Morphogenesis

Two main classes of cells in the embryo - epithelial - mesenchymal

Genomic equivalence

Differential Gene Expression

Cell differentiation can be regulated by:

- Differential gene transcription

- Selective nuclear RNA processing

- Selective messenger RNA translation

- Differential protein modification

Induction Usually involves a receptor expressed on the responding tissue and a signal (ligand) expressed by the inducing tissue Not all tissues can respond to the inductive signal - competence

Major Signaling Pathways in Development:

- Fibroblast Growth Factor (FGF) - Hedgehog - Wnt - TGF-b superfamily - Receptor tyrosine kinases - Notch - Extracellular matrix