NEURAL-TUBE EXPRESSION OF PITUITARY ADENYLATE CYCLASE-ACTIVATING PEPTIDE (PACAP) AND RECEPTOR - POTENTIAL ROLE IN PATTERNING AND NEUROGENESIS

Neural tube patterning in vertebrates is controlled in part by locally secreted factors that act in a paracrine manner on nearby cells to re gulate proliferation and gene expression, We show here by in situ hybr idization that genes for the neuropeptide pituitary adenylate cyclase- activating peptide (PACAP) and one of its high-affinity receptors (PAC (1)) are widely expressed in the mouse neural tube on embryonic day (E ) 10.5, Transcripts for the ligand are present in differentiating neur ons in much of the neural tube, whereas the receptor gene is expressed in the underlying ventricular zone, most prominently in the alar regi on and floor plate, PACAP potently increased cAMP levels more than 20- fold in cultured E10.5 hindbrain neuroepithelial cells, suggesting tha t PACAP activates protein kinase A (PKA) in the neural tube and might act in the process of patterning. Consistent with this possibility, PA CAP down-regulated expression of the sonic hedgehog- and PKA-dependent target gent gli-l in cultured neuroepithelial cells, concomitant with a decrease in DNA synthesis. PACAP is thus an early inducer of cAMP l evels in the embryo and may act in the neural tube during patterning t o control cell proliferation and gene expression.