The Journal of Neuroscience, June 15, 2001, 21(12):4373-4380
Neuronal Expression of Synaptotagmin-Related Gene 1 Is Regulated
by Thyroid Hormone during Cerebellar Development
Gregory B.
Potter,
Fabrizio
Facchinetti,
Gerard M. J.
Beaudoin III, and
Catherine C.
Thompson
Kennedy Krieger Research Institute and Department of
Neuroscience, Johns Hopkins University School of Medicine, Baltimore,
Maryland 21205
Thyroid hormone (TH) is essential for proper brain development,
acting through nuclear receptors that modulate the expression of
specific genes in response to hormone binding. In a screen for genes
regulated by TH in the rat cerebellum, we recently identified a novel
gene, synaptotagmin-related gene 1 (Srg1). The Srg1 protein is
structurally similar to synaptotagmins, a family of proteins involved
in regulating neurotransmission. To elucidate a potential role of Srg1
in brain development, we have investigated the developmental and
TH-regulated expression of Srg1 in the neonatal rat brain. We show that
expression of both Srg1 RNA and protein is detected only in the brain
and specifically in neurons. Srg1 mRNA and protein levels increase
postnatally, nearing adult levels after the third postnatal week.
Neonatal TH deficiency results in a significant reduction and delay in
expression of both Srg1 RNA and protein. Using immunohistochemistry, we
were able to detect Srg1 protein in numerous brain regions. In the
cerebellum, Srg1 protein is localized to the molecular layer,
indicating that it is highly expressed in granule cell axons. To
further examine Srg1 expression in cerebellar granule cells (CGCs), we
used an in vitro cell culture model. In primary cultures
of CGCs, Srg1 expression is significantly reduced in the absence of TH.
Srg1 mRNA is rapidly upregulated in cultured CGCs, suggesting a direct
response to TH. Neuronal and TH-regulated expression of Srg1, together
with its localization to neurites, implicates Srg1 as an important
component of the program of gene expression induced by TH in the
developing brain.
Key words:
thyroid hormone; development; cerebellum; nuclear
receptor; gene expression; synaptotagmin
Copyright © 2001 Society for Neuroscience 0270-6474/01/21124373-08$05.00/0
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