The complicated circuitry of the brain and the precise connections of groups of neurons at various places within it suggest that neurons do not randomly form synapses as they grow, but instead respond to organizing signals.

Cajal was perhaps the first scientist to observe conical, fluid projections at the ends of developing neurons, and certainly the first to posit that such a structure might be involved in guiding the neuron towards a particular target.

What we now know as growth cones – dynamic extensions of a developing neuron – respond to a variety of chemicals, secreted by target neurons and the extracellular matrix, that can be attractive or repulsive to the growth cone depending on the receptors present.

The variety of the growth cones shown above is due to the complexity of the paths they were to navigate: the ones depicted in C were travelling a quick path through white matter in the brain, while those in A and B travelled a slower, more complicated path through gray matter and the ventral commissure, respectively.

Current research has found that the shape of the growth cone in vivo differs somewhat from Cajal’s preserved specimens, but the complexity of the growth cone in relation to its travel speed remains the same.