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 regulate proliferation and gene expression. We show here by in situ hybridization that genes for the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP) and one of its high-affinity receptors (PAC1) are widely expressed in the mouse neural tube on embryonic day (E) 10.5. Transcripts for the ligand are present in differentiating neurons in much of the neural tube, whereas the receptor gene is expressed in the underlying ventricular zone, most prominently in the alar region and floor plate. PACAP potently increased cAMP levels more than 20-fold in cultured E10.5 hindbrain neuroepithelial cells, suggesting that PACAP activates protein kinase A (PKA) in the neural tube and might act in the process of patterning. Consistent with this possibility, PACAP down-regulated expression of the sonic hedgehog- and PKA-dependent target gene gli-1 in cultured neuroepithelial cells, concomitant with a decrease in DNA synthesis. PACAP is thus an early inducer of cAMP levels in the embryo and may act in the neural tube during patterning to control cell proliferation and gene expression.

[1]  A. Ruiz i Altaba,et al.  Gli1 is a target of Sonic hedgehog that induces ventral neural tube development. , 1997, Development.

[2]  A. Gurney,et al.  Control of Cell Pattern in the Neural Tube by the Zinc Finger Transcription Factor and Oncogene Gli-1 , 1997, Neuron.

[3]  R. Nusse,et al.  A Versatile Transcriptional Effector of Wingless Signaling , 1997, Cell.

[4]  E. Dicicco-Bloom,et al.  Pituitary adenylate cyclase-activating polypeptide is an autocrine inhibitor of mitosis in cultured cortical precursor cells. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Mariann Bienz,et al.  LEF-1, a Nuclear Factor Coordinating Signaling Inputs from wingless and decapentaplegic , 1997, Cell.

[6]  B. Edgar,et al.  Developmental Control of Cell Cycle Regulators: A Fly's Perspective , 1996, Science.

[7]  T. Jessell,et al.  Diversity and Pattern in the Developing Spinal Cord , 1996, Science.

[8]  Johan Ericson,et al.  Two Critical Periods of Sonic Hedgehog Signaling Required for the Specification of Motor Neuron Identity , 1996, Cell.

[9]  S. Scherer,et al.  Mutations in the human Sonic Hedgehog gene cause holoprosencephaly , 1996, Nature Genetics.

[10]  M. Scott,et al.  Antagonizing cAMP-dependent protein kinase A in the dorsal CNS activates a conserved Sonic hedgehog signaling pathway. , 1996, Development.

[11]  J. Ellison,et al.  Embryonic Expression of Vasoactive Intestinal Peptide (VIP) and VIP Receptor Genes , 1996, Journal of neurochemistry.

[12]  M. Levine,et al.  Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo. , 1996, Genes & development.

[13]  T. Jessell,et al.  Requirement for LIM Homeobox Gene Isl1 in Motor Neuron Generation Reveals a Motor Neuron– Dependent Step in Interneuron Differentiation , 1996, Cell.

[14]  H. Onda,et al.  Characterization of murine PACAP mRNA , 1995, Peptides.

[15]  A. Graham,et al.  Neural Patterning: A forward role for Hedgehog , 1995, Current Biology.

[16]  E. Zackai,et al.  Physical mapping of the holoprosencephaly critical region in 18p11.3. , 1995, American journal of human genetics.

[17]  S. Blair.  Hedgehog digs up an old friend , 1995, Nature.

[18]  T. Jessell,et al.  Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes , 1994, Cell.

[19]  S. Kondo,et al.  Characterization of epidermal cytokine profiles in sensitization and elicitation phases of allergic contact dermatitis as well as irritant contact dermatitis in mouse skin. , 1994, Lymphokine and cytokine research.

[20]  I. Black,et al.  Trophic mechanisms regulate mitotic neuronal precursors: role of vasoactive intestinal peptide (VIP) , 1994, Brain Research.

[21]  I. Tatsuno,et al.  Developmental changes of pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor in the rat brain , 1994, Peptides.

[22]  Andrew P. McMahon,et al.  Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity , 1993, Cell.

[23]  A. Graham,et al.  Even-numbered rhombomeres control the apoptotic elimination of neural crest cells from odd-numbered rhombomeres in the chick hindbrain. , 1993, Development.

[24]  U. Francke,et al.  Generation of a human chromosome 18-specific YAC clone collection and mapping of 55 unique YACs by FISH and fingerprinting. , 1993, Genomics.

[25]  S. Wank,et al.  Molecular cloning and functional expression of the pituitary adenylate cyclase-activating polypeptide type I receptor. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M. Schachner,et al.  Molecular characterization and in situ mRNA localization of the neural recognition molecule J1-160/180: a modular structure similar to tenascin , 1993, The Journal of cell biology.

[27]  E. Dicicco-Bloom,et al.  Pituitary adenylate cyclase activating polypeptide (PACAP) potently stimulates mitosis, neuritogenesis and survival in cultured rat sympathetic neuroblasts , 1992, Regulatory Peptides.

[28]  J. Drago,et al.  A method for the isolation of purified murine neuroepithelial cells from the developing mouse brain , 1991, Journal of Neuroscience Methods.

[29]  I. Tatsuno,et al.  Characterization and distribution of binding sites for the hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide. , 1990, Endocrinology.

[30]  J. Drago,et al.  Fibroblast growth factor stimulates the proliferation and differentiation of neural precursor cells in vitro , 1990, Journal of neuroscience research.

[31]  I. Black,et al.  Vasoactive intestinal peptide regulates mitosis, differentiation and survival of cultured sympathetic neuroblasts , 1990, Nature.

[32]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.