Neurotrophin-3 induced by tri-iodothyronine in cerebellar granule cells promotes purkinje cell differentiation

Dan Lindholm, Eero Castrén, Pantelis Tsoulfas, Roland Kolbeck, Maria Da Penha Berzaghi, Axel Leingärtner, Carl Philipp Heisenberg, Lino Tesarollo, Luis F. Parada, Hans Thoenen

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Abstract

Thyroid hormones play an important role in brain development, but the mechanism(s) by which triiodothyronine (T3) mediates neuronal differentiation is poorly understood. Here we demonstrate that T3 regulates the neurotrophic factor, neurotrophin-3 (NT-3), in developing rat cerebellar granule cells both in cell culture and in vivo. In situ hybridization experiments showed that developing Purkinje cells do not express NT-3 mRNA but do express trkC, the putative neuronal receptor for NT-3. Addition of recombinant NT-3 to cerebellar cultures from embryonic rat brain induces hypertrophy and neurite sprouting of Purkinje cells, and upregulates the mRNA encoding the calcium-binding protein, calbindin-28 kD. The present study demonstrates a novel interaction between cerebellar granule neurons and developing Purkinje cells in which NT-3 induced by T3 in the granule cells promotes Purkinje cell differentiation.

Original languageEnglish
Pages (from-to)443-450
Number of pages8
JournalJournal of Cell Biology
Volume122
Issue number2
StatePublished - Jul 1 1993
Externally publishedYes

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Lindholm, D., Castrén, E., Tsoulfas, P., Kolbeck, R., Berzaghi, M. D. P., Leingärtner, A., Heisenberg, C. P., Tesarollo, L., Parada, L. F., & Thoenen, H. (1993). Neurotrophin-3 induced by tri-iodothyronine in cerebellar granule cells promotes purkinje cell differentiation. Journal of Cell Biology, 122(2), 443-450.