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

Research output: Contribution to journalArticlepeer-review

164 Scopus citations


Thyroid hormones play an important role in brain development, but the mechanism(s) by which tri-iodothyronine (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 (US)
Pages (from-to)443-450
Number of pages8
JournalJournal of Cell Biology
Issue number2
StatePublished - 1993

ASJC Scopus subject areas

  • Cell Biology


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