Independent Expression of the α and β c-erbA Genes in Developing Rat Brain

Abstract

Thyroid hormone is important for normal brain development. Cellular responses to thyroid hormone are mediated by multiple nuclear receptors, classified into alpha- and beta-subtypes. In the rat, expression of both the alpha and beta genes results in several translation products. By using cRNA probes common to alpha transcripts or specific for alpha-1 and beta-1, we have studied the distribution of these transcripts in rat brain at different stages of development from embryonic day 14 to adult age by using in situ hybridization histochemistry. On embryonic day 14, the alpha-1 mRNA is already widely expressed at a low level in the developing brain. The alpha-1 mRNA is developmentally regulated and showed a peak in expression during the first 3 postnatal weeks in the cerebral cortex, amygdala, hippocampus, and cerebellum. The probe common to the alpha transcripts detected a widespread distribution and high levels of these forms in the same regions throughout postnatal development. The level of beta-1 mRNA before birth was low or undetectable. The beta-1 transcript showed developmental regulation as well, with a high level at birth in the mitral cell layer of the olfactory bulb, accumbens nucleus, caudate, and hippocampal field CA1 and increasing levels in other regions later during development. Complementary expression of the alpha and beta forms was seen in the cerebral cortex and hippocampus. The differential temporal and spatial distribution as well as coexpression at comparable levels in certain brain regions suggest different roles for the c-erbA proteins during brain development and in the mature animal.

The product of a thyroid hormone-responsive gene interacts with thyroid hormone receptors

“…In contrast, hr is predominantly expressed in brain and skin (11,13), and Hr binds to only one (TR) of several steroid and retinoid receptors tested. Hr and TR are both nuclear proteins and are coexpressed in various regions of the brain (11,33,34), suggesting that the interaction observed in vitro also occurs in vivo.…”

“…To examine the specificity of interaction between TR and Hr, Hr In addition to their interaction in vitro, Hr and TR are expressed in the same cell types in vivo. We have shown previously that hr is expressed in tissues that express TR; in situ hybridization analyses have shown that hr and TR transcripts are present in the same cell populations in the brain (11,33,34). For interaction of Hr and TR to occur in vivo, both must occupy the same subcellular compartment.…”

Genome-wide analysis of thyroid hormone receptors shared and specific functions in neural cells

“…When grafted in vivo, or when deprived of serum, they stop proliferating and differentiate into neuron-like cells within 1 wk. C17.2 cells probably originate from the cerebellum external granular layer, a transient structure populated by granular neuron precursors, and like these natural progenitors, express few if any TRs (30)(31)(32). We transfected these cells to express in a stable manner either TRα1 or TRβ1 and the reporter enhanced green fluorescent protein (Fig.…”

Regulation of Microglial Development: A Novel Role for Thyroid Hormone

“…TR␣ and TR␤ are produced in the CNS, but their patterns of expression vary markedly according to developmental stages, cell phenotype, and intracerebral localization (Bradley et al, 1989(Bradley et al, , 1992Strait et al, 1990Strait et al, , 1991Mellström et al, 1991;Puymirat et al, 1991;Puymirat, 1992;Lechan et al, 1993;Carré et al, 1998). Notably they were not detected in all neurons or macroglial cells (Puymirat et al, 1991;Puymirat, 1992).…”