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Autocrine expression and ontogenetic functions of the PACAP ligand/receptor system during sympathetic development
E DiCicco-Bloom1, P J Deutsch, J Maltzman
1Department of Neuroscience, UMDNJ/Robert Wood Johnson Medical School, Piscataway, New Jersey, 08854, USA.
Developmental Biology
|March 1, 2000
Summary
Pituitary adenylate cyclase-activating polypeptide (PACAP) significantly boosts sympathetic neurogenesis by promoting precursor mitosis and survival. This peptide is a more potent developmental signal than vasoactive intestinal peptide (VIP) in the superior cervical ganglion.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Endocrinology
Background:
- The superior cervical ganglion (SCG) is a key model for studying neural development and regulatory signals.
- Vasoactive intestinal peptide (VIP) influences sympathetic ontogeny, but its high concentration requirements suggest other ligands are involved.
- Understanding novel signaling pathways is crucial for elucidating neurogenesis processes.
Purpose of the Study:
- To investigate the expression and function of pituitary adenylate cyclase-activating polypeptide (PACAP) during SCG development.
- To determine PACAP's role in sympathetic neurogenesis, comparing its potency to VIP.
- To explore PACAP's effects on precursor proliferation, survival, and neuronal differentiation.
Main Methods:
- Detection of PACAP and PACAP receptor (PAC1) mRNA in vivo during SCG ontogeny (E14.5-E17.5).
- In vitro culture of SCG precursors exposed to PACAP and VIP peptides.
- Assays for mitogenic activity, precursor survival, neurite outgrowth, and neurotrophin receptor expression (trkC, trkA).
- Analysis of intracellular signaling pathways (cAMP, PI, Ca2+).
Main Results:
- PACAP and PAC1 receptor mRNA are expressed in SCG precursors during proliferation.
- PACAP significantly increased precursor mitogenesis (4-fold) and survival (>2-fold), acting via PAC1 receptors.
- PACAP demonstrated 1000-fold higher potency than VIP, suggesting it is the primary developmental signal.
- PACAP promoted neuronal differentiation, increasing neurite outgrowth (4-fold) and enhancing trkC/trk A expression.
Conclusions:
- PACAP plays critical roles in sympathetic neurogenesis, acting as a potent mitogenic and survival factor for SCG precursors.
- PACAP is a more significant developmental signal than VIP in the SCG, primarily signaling through PAC1 receptors.
- The PACAP signaling system likely exerts an autocrine function during sympathetic neurogenesis, influencing proliferation, survival, and differentiation.