Neuronal sources of <i>hedgehog</i> modulate neurogenesis in the adult planarian brain.

Abstract

The asexual freshwater planarian is a constitutive adult, whose central nervous system (CNS) is in a state of constant homeostatic neurogenesis. However, very little is known about the extrinsic signals that act on planarian stem cells to modulate rates of neurogenesis. We have identified two planarian homeobox transcription factors, <i>Smed-nkx2.1</i> and <i>Smed-arx</i>, which are required for the maintenance of cholinergic, GABAergic, and octopaminergic neurons in the planarian CNS. These very same neurons also produce the planarian <i>hedgehog</i> ligand (<i>Smed-hh</i>), which appears to communicate with brain-adjacent stem cells to promote normal levels of neurogenesis. Planarian stem cells nearby the brain express core <i>hh</i> signal transduction genes, and consistent <i>hh</i> signaling levels are required to maintain normal production of neural progenitor cells and new mature cholinergic neurons, revealing an important mitogenic role for the planarian <i>hh</i> signaling molecule in the adult CNS.