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The Journal of Neuroscience, August 15, 1999, 19(16):6979-6993

Thyroid Hormone Regulates reelin and dab1 Expression During Brain Development

Manuel Alvarez-Dolado^{1, 2}, Mónica Ruiz², José A. Del Río², Soledad Alcántara², Ferran Burgaya², Michael Sheldon³, Kazunori Nakajima⁴, Juan Bernal¹, Brian W. Howell⁵, Tom Curran³, Eduardo Soriano², and Alberto Muñoz¹

¹ Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, 28029 Madrid, Spain, ² Department of Animal and Plant Cell Biology, University of Barcelona, Barcelona 08028, Spain, ³ Department of Developmental Neurobiology, St. Jude Research Children's Hospital, Memphis, Tennessee 38105, ⁴ Department of Molecular Neurobiology, Institute of DNA Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan, and ⁵ Fred Hutchinson Cancer Research Center, Seattle, Washington 98109

The reelin and dab1 genes are necessary for appropriate neuronal migration and lamination during brain development. Since these processes are controlled by thyroid hormone, we studied the effect of thyroid hormone deprivation and administration on the expression of reelin and dab1. As shown by Northern analysis, in situ hybridization, and immunohistochemistry studies, hypothyroid rats expressed decreased levels of reelin RNA and protein during the perinatal period [embryonic day 18 (E18) and postnatal day 0 (P0)]. The effect was evident in Cajal-Retzius cells of cortex layer I, as well as in layers V/VI, hippocampus, and granular neurons of the cerebellum. At later ages, however, Reelin was more abundant in the cortex, hippocampus, cerebellum, and olfactory bulb of hypothyroid rats (P5), and no differences were detected at P15. Conversely, Dab1 levels were higher at P0, and lower at P5 in hypothyroid animals.

In line with these results, reelin RNA and protein levels were higher in cultured hippocampal slices from P0 control rats compared to those from hypothyroid animals. Significantly, thyroid-dependent regulation of reelin and dab1 was confirmed in vivo and in vitro by hormone treatment of hypothyroid rats and organotypic cultures, respectively. In both cases, thyroid hormone led to an increase in reelin expression. Our data suggest that the effects of thyroid hormone on neuronal migration may be in part mediated through the control of reelin and dab1 expression during brain ontogenesis.

Key words: reelin, dab1, thyroid hormone, neuronal migration, cortical lamination, brain development

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19166979-15$05.00/0

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