PS/ Limb Formation

The Biology

In the early embryo the arms and legs have yet to form. This begins at ~ 6 weeks, when they develop from four outgrowths or buds. The two upper buds will form the arms while the two lower buds become the legs.

Fingers and toes resolve in the limb buds as development proceeds. This involves the programmed death of intervening cells.

Film: Limb bud outgrowth simulation, James Sharpe, CGR, Barcelona,
The role of spatially controlled cell proliferation in limb bud morphogenesis, PLoS Biology, 2010 Jul 13;8(7):e1000420)
Image 1. Scanning electron micrograpgh of mouse embryo, © Wellcome Images
Image 2. Fingers emerging in the developing hand-plate, © Kate Storey

How it works

To make a hand or foot requires signals that promote outgrowth of the limb bud and signals that define where the fingers or toes will form. Outgrowth is promoted by a growth factor called Fibroblast growth factor, which is produced by cells at the tip of the limb bud.

Image.Expression of an FGF gene (blue) at the tip of the early limb bud.
image © Kate Storey

Cells in the lower rim of the bud serve as source of another protein, called Sonic hedgehog (Shh). Cells close to this source form the little finger or toe, while the thumb or big toe are formed by cells furthest away, which are exposed to the least Shh protein.

Find out more:
A brief overview of limb development

Key labs that work on Limb development:
James Sharpe, Centre for Genomic regulation, Barcelona

Cliff Tabin, Harvard Medical School

Neil Vargison, University of Aberdeen

Malcolm Logan, MRC, National Institute for Medical Research, UK

Selected research papers:

A review that addresses how growth and patterning of the limb are integrated

A review of the generation of pattern and form in the developing limb

Mechanism of limb bud initiation

Modelling digit formation

When development goes wrong

In rare cases, babies are born missing all or parts of a limb. Around 20% of such occurrences are due to genetic defects. Others are caused by environmental influences, such the drug thalidomide.

This was prescribed to women in the 1950’s and 60’s to relieve morning sickness, but was found to inhibit limb outgrowth. How the drug causes these defects is an area of active research.

Find out more:
National Institute of Child Health – US based research centre focussing on child health and developmental defects

The Thalidomide Society – UK based, supports families and adults affected by thalidomide

BBC Interview with Neil Vargesson - a young researcher investigating the action of thalidomide

Limb bud formation dress: Details

Limb bud dress: Cotton canvas, oil paint

This dress, made of artist’s primed canvas, was painted in oils to show the digits forming within the expanding buds, by Chloe Sendall.

Drawing
1997
Copyright Helen Storey