Module : Development of the Nervous System

Lecture 5

Target selection & topographic maps

Benson DL et al., 2001

Targeting involves decisions at many scales

Target selection

Involves pruning of initially mis-targeted processes.

Invovles competition for space

Involves chemoattractants and chemorepellents.

Somatotopic organization in the cortex. The organization of the cortex was determined by electrically stimulating human patients during neurosurgery. Muscles involved in making skilled movements are dispropotionately represented.

Correspondence between bristles and barrel fields in the somatosensory cortex.

Plasticity can lead to large scale remapping

Experiments conducted by Sperry in 1943 lead to the hypothesis of chemoaffinity for target selection

Topographic mapping is different in different systems. The first creates a central representation of visual space while the second leads to an odor representation map.

The development of the stripped carpet assay was crucial in dissecting the molecular basis for target selection and topographic maps.

A stripped carpet assay experiment to show that temporal but not nasal axons are repulsed by a cue present in the posterior tectal membrane.

The Ephrins are membrane associated guidance molecules that are classified on the basis of their membrane association.

Ephrin A are tethered to the membrane by a Glycosylphosphatidylinositol (GPI) link.

Ephrin B are transmembrane proteins with a cytoplasmic domain.

The Eph proteins are transmembrane proteins with a tyrosine kinase domain and form a large family.

Ephrin/Eph complexes signal bidirectionally.

Gradients of Eph and Ephrins can in principle specify the topographic map of retinotectal projections.

One can coat stripes with different candidate guidance and analyze the outgrowth of nasal and temporal axons.

Gene knockout studies followed by labeling of nasal and tectal axons can help identify cues that are important in building topographic maps

Examples of reverse and forward signaling

The problem of growth – the Eph and ephrin gradients regulate as the retina and tectum grow

Selection of target involves several stages.

Axons have to find their way to the general target area.

Within the area they have to find the correct location within that area

Each system has its own topographic map – contrast the visual versus the odorant maps.

The gradient of Eph and ephrin molecules are important in specifying the retinotectal map.

The central maps established during development are not static and can change depending on the environment. This also includes events such as injury.