Development in the absence of skeletal muscle results in the sequential ablation of motor neurons from the spinal cord to the brain

Mice lacking the transcription factors Myf-5 and MyoD lack all skeletal mus cle and therefore present a unique opportunity to investigate the dependenc e of nervous system development on myogenesis. Motor neurons arose normally in the spinal cord of mutant embryos and by birth all somatic motor neuron s were eliminated by apoptosis. By contrast, interneurons were not affected . Proprioceptive sensory neurons in the dorsal root ganglia underwent apopt osis. The facial motor nucleus was ablated of motor neurons and contained l arge numbers of apoptotic bodies. Surprisingly, giant pyramidal neurons wer e absent in the motor cortex without any corresponding evidence of apoptosi s. The epaxial and cutaneous component of dorsal ramus failed to form in th e absence of the myotome. Therefore, we conclude that nervous development i s more intimately coupled to skeletal myogenesis than has previously been u nderstood. (C) 1999 Academic Press.