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The PACAP ligand/receptor system regulates cerebral cortical neurogenesis
E Dicicco-Bloom1, N Lu, J E Pintar
1Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway, USA. diciccem@umdnj.edu
Annals of the New York Academy of Sciences
|February 3, 1999
Summary
Pituitary adenylate cyclase-activating polypeptide (PACAP) signaling inhibits neural stem cell division, promoting neuronal differentiation. This process is crucial for determining neuron fate and laminar position during brain development.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- The pituitary adenylate cyclase-activating polypeptide (PACAP) ligand/type I receptor system is present in the embryonic nervous system, indicating potential roles in neural development.
- Cerebral cortex precursor cells exit the cell cycle at specific times, which dictates their final neuronal fate and laminar position.
- Mitogenic factors like bFGF and IGF-I promote precursor proliferation during cortical neurogenesis.
Purpose of the Study:
- To investigate the role of PACAP signaling in regulating cortical precursor cell cycle exit and neuronal differentiation.
- To determine if PACAP acts as an anti-mitogenic signal antagonizing growth factors during embryonic brain development.
Main Methods:
- Inhibition of [3H]thymidine incorporation in embryonic day 13.5 rat cortical precursors.
- Assessment of mitotic cell proportion and morphological/biochemical differentiation markers.
- In vivo and in vitro analysis of PACAP and its receptor expression in cortical precursors.
- Use of peptide antagonists to study the effect on precursor proliferation.
Main Results:
- PACAP significantly inhibited cortical precursor proliferation and reduced the number of mitotic cells.
- PACAP treatment promoted neuronal differentiation, evidenced by morphological and biochemical changes.
- PACAP ligand and receptor were co-expressed in mitotic precursors, suggesting autocrine signaling.
- Blocking PACAP signaling with antagonists led to increased precursor proliferation.
Conclusions:
- PACAP signaling acts as a crucial inhibitory signal, antagonizing mitogenic factors to induce cell cycle exit in cortical precursors.
- PACAP-induced cell cycle withdrawal is coupled with neuronal differentiation, influencing neuronal phenotype and laminar positioning.
- The interplay between PACAP and mitogenic signals regulates the precise timing of cell cycle exit during cortical development.