Development in the Absence of Skeletal Muscle Results in the Sequential Ablation of Motor Neurons from the Spinal Cord to the Brain

Abstract

Mice lacking the transcription factorsMyf-5andMyoDlack all skeletal muscle and therefore present a unique opportunity to investigate the dependence of nervous system development on myogenesis. Motor neurons arose normally in the spinal cord of mutant embryos and by birth all somatic motor neurons were eliminated by apoptosis. By contrast, interneurons were not affected. Proprioceptive sensory neurons in the dorsal root ganglia underwent apoptosis. The facial motor nucleus was ablated of motor neurons and contained large numbers of apoptotic bodies. Surprisingly, giant pyramidal neurons were absent in the motor cortex without any corresponding evidence of apoptosis. The epaxial and cutaneous component of dorsal ramus failed to form in the absence of the myotome. Therefore, we conclude that nervous development is more intimately coupled to skeletal myogenesis than has previously been understood.