LIMitless Combinations?

Sonic Hedgehog (Shh) is produced by Purkinje neurons during the developmental stage when they are extending their dendritic tree LIMitless Combinations? and beginning to form synaptic connections with the axons of granule neurons. Granule cell precursors bind Shh via the protein Patched (Ptc), which releases Ptc's inhibition of smoothened and induces a cascade of signals leading to proliferation. Granule cells During development, motor neurons project their axons later exit the cell cycle, extend neurites, and form synaptic connec-to a large variety of targets. In vertebrate embryos, these tions with Purkinje cells. Thus, Purkinje cells appear to control the targets include branchial arch–derived muscles, axial number of granule cells entering the cerebellar circuit. and body wall muscles, limb muscles, and autonomic ganglia. Different kinds of targets are innervated by motor neurons that occupy distinct rostrocaudal and dorso-status. The final proof of a role for Shh was provided by studies with blocking antibodies against Shh (Ericson ventral positions within the central nervous system. For example, cell bodies of motor neurons that innervate et al., 1996). When hybridoma cells secreting blocking antibodies were injected into animals in the early post-axial muscles lie in medial positions of the ventral spinal cord, whereas motor neurons that innervate limb mus-natal period, the mitotic zone of the EGL thinned from 8–10 cells to 2–3 cells deep. These studies provided cles are located more laterally at the levels of the fore-limb and hindlimb (Tsuchida et al., 1994). Stereotyped evidence that Shh functions in the expansion of the pool of neuronal precursor cells in the EGL. relationships between motor neurons and targets also exist for invertebrate embryos: in Drosophila melano-In this paper, we see the first evidence for the molecular basis of a signaling loop between Purkinje cells and gaster, motor neurons that occupy characteristic positions within the ventral nerve cord (VNC) project axons granule cells that may act to control the number of granule neurons. This is a remarkable finding, because it to particular abdominal body wall muscles (Landgraf et al., 1997). suggests that the control of the formation of neural circuits commences much earlier than previously imagined. Motor neurons that have common cell body positions and axon projections also express common genes. In Whereas previous models held that neuronal number is controlled by programmed cell death after synaptic particular, subclasses of vertebrate motor neurons express cell type–specific combinations of genes encod-connections form, Wechsela-Reya and Scott show that …