Positionally selective growth of embryonic spinal cord neurites on muscle membranes

Motor neurons from distinct positions along the rostrocaudal axis generally innervate muscles or muscle fibers from corresponding axial levels. These topographic maps of connectivity are partially restored after denervation o r transplantation under conditions in which factors of timing and proximity are eliminated. It is therefore likely that motor neurons and some intramu scular structures bear cues that bias synapse formation in favor of positio nally matched partners, To localize these cues, we studied outgrowth of neu rites from embryonic spinal cord explants on carpets of membranes isolated from perinatal rat muscles. Neurites from rostral (cervical) and caudal (lu mbar) spinal cord slices exhibit distinct growth preferences. In many insta nces, rostrally derived neurites grew selectively on membranes from forelim b muscles or from a single thoracic muscle (the serratus anterior) when giv en a choice between these membranes and membranes from hindlimb muscles or laminin, Caudally derived neurites almost never exhibited such rostral pref erences, but instead preferred membranes from hindlimb muscles or a single hindlimb muscle (the gluteus) to rostral muscles or laminin. Likewise, spin al neurites exhibited distinct position-related preferences for outgrowth o n membranes of clonal myogenic cell lines derived from specific rostral and caudal muscles. Taken together these results suggest that the membranes of motor axons and myotubes bear complementary labels that vary with rostroca udal position and regulate neuromuscular connectivity.