Guidance at the construction site, the role of axon guidance molecules in postnatal development of the hippocampus

Abstract

Precise wiring of neuronal networks during development is of utmost importance regarding the function of the network. This becomes apparent if one studies the etiology of various neurological diseases such as autism, epilepsy, or schizophrenia, in which alteration in hippocampal network wiring is related to the development of these pathologies (Eastwood et al., 2003; Gant et al., 2008; Holtmaat et al., 2003). The objective of the present work is to provide an overview on the molecular mechanisms that support the development of the hippocampus. Specialized families of proteins, called axon guidance molecules (AGMs), provide these molecular mechanisms and have been studied in the past decades in relation to network wiring. Interestingly the development of the hippocampus as well as the activity of these AGMs continues postnatally (Nadel and Willner, 1989; Skutella and Nitsch, 2001). For these reasons the scope of the present work is the involvement of AGMs in hippocampal development from postnatal day 0 to 28 (P0-28). Three major conclusions can be drawn from the reviewed work; 1) Several AGMs are important for the laminar organization of the hippocampus. 2) Support from, in particular, Eph-ephrin complexes and semaphorins are needed to convey the process of synaptogenesis and maturation. 3) The specific temporo-spatial expression of AGMs correlates with the establishment of innervation from specific input regions. Alteration in expression of these AGMs impacts the timing and spatial distribution of specific projections.