Introduction to Developmental Biology

January 12, 2009

The following slides….

• This material is intended to show you the level of knowledge that you will need master for any given topic– It is NOT what you should already know, but

you should have the background enabling you to learn this material

• We will go over material from Gilbert and from other sources when additional information is needed for illustration and clarity

• Developmental processes include– Gamete formation, fertilization– Embryogenesis– Metamorphosis– Sexual maturation– Wound healing– Tissue, organ regeneration– Stem cell behavior– Many cancers

An Introduction to Embryonic Development

• Developmental programs– Internally programmed– Induced

• Cell-Cell interactions– Junctions and adhesion molecules– Signaling through secreted factors or membrane-

tethered molecules• Cell-Extracellular matrix interactions

– Integrins and adhesive specializations• Cell and tissue reorganization

– Epithelial-Mesenchymal Transformation (and/or back)

What regulates development?

An Example of material covered

• Epithelial/Mesenchymal Transformation– Rearranging cells and tissues to build

structures and organs• Epithelial Mesenchymal Interactions

– Changing the differentiated state of cells and tissue through an exchange of signals between adjacent tissues

Epithelial-mesenchymal Interactions• Chapter 6, 15 Gilbert• Progressive interactions of tissues through cell-cell interactions

mediated by:– Direct contact

• CAMS• Cadherins• Junctions• Notch/delta type interactions

– ECM• Matrix to matrix• Integrins

– Secreted growth factors– Shh– Wnt– FGFs– TGF-βs– BMPs

• Specific receptors

E.D. Hay

Epithelia: Cell sheets, tubes or cords of cells with basal lamina and subapical junctional complexes

-Apical/Basal Polarity

Basal Lamina

Basal Lamina

You will need to understand the relationship between organelle structure and cell/tissue function

Integrin binding induces formation of a focal adhesion

www.steve.gb.com

Focal adhesions bind actin filaments. The focal adhesions are joined by hemidesmosomes, which associate with intermediate filaments

actin

Inter. Fil.

http://oregonstate.edu/instruction/bb450/lecturenoteskevin/cellularsignalingoutline.html

Receptor tyrosine kinase activity

Ras and Growth Factors

You will need to learn and understand signaling pathways

You will need to be able to learn and understand structure and function of ECM

Fibronectin: two 220 kDa chains, multiple binding domains.

Binds the Integrin

• You will need to apply these facts, functions and mechanisms to synthesize an understanding of increasingly complex systems as the semester goes on.

Induction and response

• There are inducing tissues that produce a signal and

• Responding tissues that make some change in response to the signal

• In order to respond a tissue must be competent– State of differentiation– Presence of receptors

• Mutual interactions can occur simultaneously (limb, kidney) or sequentially (teeth)

Instructive vs Permissive

• If a signal from one cell/tissue is required for the response of a target cell/tissue, that is called an Instructive Interaction

• If a tissue has all of the factors it needs to develop/differentiate within itself and only needs an enviornment that allows intrinsic processes to occur, that is called a Permissive Interaction

Some interactions are epithelial/epithelial, some epithelial/mesenchymal

Example of instructive interaction: epithelial/epithelial

Progressive interactions in eye development

Shows interaction between the optic vesicle and the lens placode to induce lens formation. Then an interaction between lens and prospective retina affecting neural retinal development. --Mutual interaction

• But the optic vesicle/lens placode interaction is not the start of the inductive cascade….

Lens induction in newts

Progressive interactions in lens induction

• Inducers have additive effect• Order of tissues with inductive capacity:

– Pharyngeal endoderm– Cardiac mesoderm– Optic vesicle

• The lens epithelium must be competent to respond-role of Pax6:

-Pax 6 expression occurs if the early inductive interactions have occurred

-as long as the lens/surface ectoderm can express Pax 6, then the lens can form

Competence and lens induction: role of Pax6

You will need to learn about patterning genes

Progressive interactions in eye development

Must be Pax6 positive

Feather formation: epithelial/mesenchymal between the skin ectoderm and dermis

Classical Example of Epithelial/Mesenchymal Interaction

Feather germ formation and development

• The epidermis makes the skin appendage (feather, etc), but the type of appendage made is determined by instructions from the dermis in different regions of the body

• If epidermis from the wing is paired with dermis from the leg, scales will form instead of feathers

• Studying feather and scale formation in chick in detail shows a more complicated explanation and a potential role of the epidermis. – Combining feather-region epidermis with 13-day chick embryo

tarsometatarsal dermis forms scales. – However, when recombined the same epidermis with a 10-day

tarsometatarsal dermis it forms feathers. – This means that the dermis acquires it inductive ability gradually

and the epidermis has an inherent identity that can be overcome by competent dermis

– FGF3 and 10 are produced by the dermis in the area where a feather will be induced

Mouse feathers

• It is possible to combine chick skin epidermis that will form feathers with pre-instructive dermis from mouse and the mouse dermis will “go along” with the program of the skin to make mouse feathers (Dhouailly)

Overall Goal of K331

• We will learn about processes and mechanisms used in the formation and development of many tissues and organs

• We will examine the formation of embryonic germ layers, tissues and organs, giving you a basic foundation in Developmental Biology– But NOT all of the organs in the body

• By studying a range of tissues and organs you will develop the tools to study any tissue or organ development