Axonal growth and fasciculation linked to differential expression of BDNF and NT3 receptors in developing cerebellar granule cells

• Published in: The Journal of neuroscience Vol. 15; no. 7; pp. 4970 - 4981
• Main Authors: Segal, RA, Pomeroy, SL, Stiles, CD
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01.07.1995; Society for Neuroscience
• Subjects: Animals; Axons - physiology; Brain-Derived Neurotrophic Factor; Cerebellum - cytology; Cerebellum - growth & development; Cerebellum - physiology; GAP-43 Protein; Growth Substances - metabolism; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred BALB C; Nerve Growth Factors - pharmacology; Nerve Growth Factors - physiology; Nerve Tissue Proteins - metabolism; Nerve Tissue Proteins - pharmacology; Nerve Tissue Proteins - physiology; Neurites - drug effects; Neurites - physiology; Neurotrophin 3; Receptor Protein-Tyrosine Kinases - metabolism; Receptor Protein-Tyrosine Kinases - physiology; Receptor, Ciliary Neurotrophic Factor; Receptor, trkC; Receptors, Nerve Growth Factor - metabolism; Receptors, Nerve Growth Factor - physiology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.15-07-04970.1995

In the developing cerebellum, young granule neurons in the external germinal layer respond preferentially to BDNF, while mature neurons within the inner portion of the cerebellum respond preferentially to NT3. Here we show that this anatomic distinction reflects a developmentally regulated switch at the level of neurotrophin receptor gene expression. The salient feature of the developmental switch is a change in the ration of mRNA transcripts encoding functional BDNF and NT3 receptor tyrosine kinases. The ratio of the BDNF receptor trkB to the NT3 receptor trkC reverses from 5:1 in neonatal cerebellum to 1:3 in adult cerebellum. TrkB and TrkC are closely related transmembrane tyrosine protein kinases. However, activation of BDNF and NT3 receptors in cerebellar granule neurons do not give equivalent biological responses. In aggregate cell culture and single cell assays, BDNF enhances axonal outgrowth of early granule cells by influencing neurite elongation. In contrast, NT3 alters the morphology of outgrowth. Collectively, these findings suggest that regulation of neurotrophin receptors during cerebellar development is important for the timing and morphology of axonal growth.