Int. J. Dev. Biol. 46: 551 - 558 (2002)

Vol 46, Issue 4

Special Issue: Developmental Biology in Australia and New Zealand

Elucidating the molecular mechanisms that underlie the target control of motoneuron death

Published: 1 July 2002

Glen B Banks and Peter G Noakes

Department of Physiology/Pharmacology, School of Biomedical Sciences, and SRC Bioinformatics and Applied Genomics, University of Queensland, Australia. Banks@plpk.uq.edu.au

Abstract

Approximately half of the motoneurons generated during normal embryonic development undergo programmed cell death. Most of this death occurs during the time when synaptic connections are being formed between motoneurons and their target, skeletal muscle. Subsequent muscle activity stemming from this connection helps determine the final number of surviving motoneurons. These observations have given rise to the idea that motoneuron survival is dependent upon access to muscle derived trophic factors, presumably through intact neuromuscular synapses. However, it is not yet understood how the muscle regulates the supply of such trophic factors, or if there are additional mechanisms operating to control the fate of the innervating motoneuron. Recent observations have highlighted target independent mechanisms that also operate to support the survival of motoneurons, such as early trophic-independent periods of motoneuron death, trophic factors derived from Schwann cells and selection of motoneurons during pathfinding. Here we review recent investigations into motoneuron cell death when the molecular signalling between motoneurons and muscle has been genetically disrupted. From these studies, we suggest that in addition to trophic factors from muscle and/or Schwann cells, specific adhesive interactions between motoneurons and muscle are needed to regulate motoneuron survival. Such interactions, along with intact synaptic basal lamina, may help to regulate the supply and presentation of trophic factors to motoneurons.