MRC National Institute for Medical Research, London
Science for Health
Malcolm Logan group project:
Dissecting the mechanisms that regulate vertebrate limb development
Initiation of the limb bud
The first step in limb formation is an inductive signal from the main body axis acting on adjacent cells at specific regions along the flank of the main body. In order for the prospective limb-forming regions to respond to an instructive signal they must be competent to receive such cues. We aim to understand how these regions are made competent to respond to instructive cues and how these regions of competence are correctly positioned along the main body axis.
Specification of limb-type specific morphologies
During limb bud initiation, cells in the prospective forelimb-forming region respond to generate one type of limb element, an arm, while cells in the hindlimb-forming region respond to produce a different limb-type, a leg. An area of great interest is therefore how the same signal that initiates limb outgrowth can elicit the formation of two distinct structures, an arm in one case and a leg in the other. We are interested in studying genes that are activated, or 'expressed', exclusively in either the developing forelimb or the developing hind limb since this limb-type restricted expression pattern is highly suggestive that the gene may play an important role determining the differences between arms and legs. Two evolutionarily related, so called 'T-box' genes, Tbx5 and Tbx4, are expressed in a restricted manner in either the developing forelimb or hindlimb, respectively. Another gene, named Pitx1, is expressed in the developing hindlimb but not the forelimb. All three of these genes produce proteins that control the switching on or off of other genes. We are therefore interested in identifying the targets of Tbx5, Tbx4 and Pitx1.
Click image to view at full-size
Whole mount in situ hybridisation showing the expression patterns of three genes that are involved in specifying limb-type identity. Tbx5 is expressed in the forelimb and not the hindlimb. While Tbx4 and Pitx1 are both expressed exclusively in the developing hindlimb and not the forelimb.
Morphogenesis of the limb
Some genes have limb-type restricted gene expression patterns. Their mRNA transcripts are present in either the forelimb or hindlimb. The arms and legs are homologous structures comprised of the same bone, muscle and tendon tissue-types. The elements in the hand share obvious morphological and functional similarities to those of the foot. Each is clearly distinct however and is fashioned to perform a function characteristic to the limb to which it belongs. We are interested in understanding the processes that operate to produce the distinct morphology of tissues in the arms and legs. How are the characteristic shapes of the humerus and femur bones produced? How are the patterns of distinct muscles bundles present in the arms and legs produced?
Logan group
Recent publications
Research projects
- Dissecting the mechanisms that regulate vertebrate limb development
- Developing 3D imaging techniques to study limb development
- Interactive mouse 3D Limb Anatomy Atlas
Gallery
© MRC National Institute for Medical Research
The Ridgeway, Mill Hill, London NW7 1AA
Top of page