Neuronal expression of synaptotagmin-related gene 1 is regulated by thyroid hormone during cerebellar development.
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.
Potter
G B
GB
Kennedy Krieger Research Institute and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Facchinetti
F
F
Beaudoin
G M
GM
Thompson
C C
CC
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008713:Methimazole; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D050857:Synaptotagmins; D013963:Thyroid Hormones / Q000172:deficiency / Q000378:metabolism* / Q000494:pharmacology; D033921:Vesicular Transport Proteins
D008565:Membrane Proteins; D012333:RNA, Messenger; C512777:Syt12 protein, rat; C424133:Sytl1 protein, mouse; D013963:Thyroid Hormones; D033921:Vesicular Transport Proteins; D050857:Synaptotagmins; D008713:Methimazole