Building an Organism: Genes, Cells and

Development

Prof. Gareth I. Jenkins Gareth.Jenkins@glasgow.ac.uk

How is a complex multicellular organism produced - how does it develop and function?

Aims of the Course:

Three key aims are to: provide a basic understanding of the developmental processes that produce multicellular organisms provide information on key cellular processes how cells divide, differentiate, perceive external stimuli and communicate show that genes produce molecular instructions that determine the organisation and behaviour of multicellular organisms

An introduction to Molecular and Cellular Biology

21 lectures + 1 lab

Assessment: Class exam 15% Laboratory 15% Degree exam 70%

How to be successful

Engage in lectures Use forum and contact staff

Attend lectures and lab

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Lecture 1

Introduction to Development

1. What is development? 2. How is development controlled? 3. How can we discover the cellular and

molecular mechanisms responsible for development?

1. What is development?

Some definitions:

Development: change with time Growth: increase in size

- Morphogenesis: shape or form - Differentiation: specialisation

male gamete

Development proceeds in the context of the life cycle:

female gamete

fertilisation

zygote

embryogenesis

adult

The purpose is reproduction

Big Question:

How does a single celled zygote become a complex multicellular organism with specialised cells, tissues and organs?

Embryonic development of the zebrafish

Some key processes:

Development of cell polarity: acquisition of assymetry

Animal pole

Vegetal pole Amphibian oocyte Algal zygote

Determines subsequent fate

How is polarity established?

Becoming multicellular Early stages in starfish development

Unfertilised egg

2-cell stage 4-cell stage

16-cell stage 32-cell stage

How is cell division controlled?

leaf epidermis

What causes cells to commit to particular developmental fates?

Pattern formation, cell commitment, cell fate

Insect varvae

Organogenesis

Fly head

How are complex organs produced with the right number and spatial distribution of parts?

Differentiation

How do genes determine the specialisation of cell function?

2. How is development controlled?

Some aspects of regulation at the cellular level:

Control of cell size and shape Control of cell division

Cell movement and adhesion

Communication between cells

Acquisition of polarity

Responses to external stimuli

Genetic basis:

Genes specify the developmental blueprint

Some genes are expressed as a consequence of a developmental change

Some genes control development: e.g. some transcription factors determine cell commitment and organogenesis What is a transcription factor?

The expression of many genes is regulated e.g. in specific cell types, at particular times in development, or in response to external stimuli:

differential gene expression

This is a key factor in controlling development

3. How can we discover the cellular and molecular mechanisms

responsible for development?

To understand how development is controlled we need to: establish how processes involved in development are regulated within cells identify genes controlling development and determine the functions of the proteins they encode determine how expression of genes controlling development is regulated

Imaging cellular processes Based on the power of microscopy

Identify gene that has become mutated

Based on the power of genetics

Isolate mutant in selected process

Draw conclusions on gene function

Wild-type! apetala3!

Determining gene function

The forward genetic approach

Antennapedia

Gene/protein sequence provides information on cellular function

Model organisms:

Yeast

Mouse

Selected for their suitability for the molecular genetic approach

Zebra fish

Caenorhabditis

Arabidopsis

Drosophila

Advantages of model organisms for genetics

1. Small and easy to grow

2. Rapid generation time 3. Lots of progeny from each individual 4. Preferably self fertile and able to be crossed 5. Easy to produce mutants

Advantages for molecular biology

1. Small genome - enables full genome sequence to be obtained and helps gene isolation

2. Easy to genetically transform

3. Methods for isolating genes corresponding to mutants

What is a genome?

Small genome enables full genome sequence to be obtained and helps gene isolation

Genome sizes: mega base pairs

E.coli 4.6 Yeast 12 Caenorhabditis 97 Arabidopsis 120 Drosophila 132 Zebrafish 1600 Mouse 2200 Human 3300

The combination of excellent genetics the advantages for molecular biology has determined the selection of model organisms

Small bacteriovorous nematode Simple development programme: lineages of cells Usually self-fertilising hermaphrodites Life cycle ~3 days Easy to produce mutants Genome fully sequenced

Caenorhabditis elegans

Fruit fly Studies on e.g. control of segmentation

in larvae Male and female flies Life cycle ~2 weeks Easy to produce mutants Genome fully sequenced

Drosophila melanogaster

Arabidopsis thaliana Small flowering plant Self- and cross-fertile Life cycle ~6 weeks Easy to produce mutants Genome fully sequenced Very easy to genetically transform