Related Experiment Video
Updated: Aug 7, 2026
Ex Vivo Culture of Chick Cerebellar Slices and Spatially Targeted Electroporation of Granule Cell Precursors
Published on: December 14, 2015
Microarray analysis of knockout mice identifies cyclin D2 as a possible mediator for the action of thyroid hormone
Anne-Lise Poguet1, Claude Legrand, Xu Feng
1Laboratoire de Biologie Moléculaire et Cellulaire de l'Ecole Normale Supérieure de Lyon UMR CNRS 5665 LA INRA913, 46 Allée d'ltalie 69364 Lyon CEDEX07France.
Abstract:
Thyroid hormone is a major regulator of postnatal brain development, but the precise molecular mechanisms underlying its action in this organ remain poorly understood. We used microarray analysis to identify new target genes in brain. Thyroid hormone treatment of hypothyroid Pax8(-/-) knockout mice, which lack thyroid follicular cells, had a very limited global effect on brain transcripts. This analysis mainly identified cyclin D2 as a new thyroid hormone target gene in the cerebellum of hypothyroid mice. Thyroid hormone receptor (TRalpha and/or TRbeta) knockout mice studies provided further genetic evidence that cyclin D2 is likely to mediate the antiapoptotic effect exerted by thyroid hormone on the cerebellum external granular layer neuroblasts but that this transcriptional activation is not directly exerted by the thyroid hormone receptors.
Insights
Thyroid hormone is crucial for brain development. This study identifies cyclin D2 as a new target gene, potentially mediating thyroid hormone
Area of Science:
- Neuroscience
- Endocrinology
- Molecular Biology
Background:
- Thyroid hormone plays a critical role in postnatal brain development.
- The specific molecular pathways of thyroid hormone action in the brain are not fully understood.
- Identifying novel target genes is essential for elucidating these mechanisms.
Purpose of the Study:
- To identify new thyroid hormone target genes in the brain using a comprehensive approach.
- To investigate the role of cyclin D2 in thyroid hormone-mediated effects on brain development.
- To determine the directness of thyroid hormone receptor involvement in regulating cyclin D2 expression.
Main Methods:
- Microarray analysis was employed to screen for differentially expressed genes in the brain.
- Studies utilized hypothyroid Pax8(-/-) knockout mice lacking thyroid follicular cells.
- Thyroid hormone receptor (TRalpha and/or TRbeta) knockout mouse models were used for genetic validation.
Main Results:
- Thyroid hormone treatment showed limited global effects on brain transcripts in hypothyroid mice.
- Cyclin D2 was identified as a novel thyroid hormone target gene, particularly in the cerebellum.
- Evidence suggests cyclin D2 mediates thyroid hormone's antiapoptotic effects on cerebellar neuroblasts, but not via direct transcriptional activation by thyroid hormone receptors.
Conclusions:
- Cyclin D2 is a newly identified thyroid hormone target gene in the developing cerebellum.
- Cyclin D2 likely mediates the antiapoptotic actions of thyroid hormone on cerebellar neuroblasts.
- The transcriptional regulation of cyclin D2 by thyroid hormone receptors is indirect, highlighting complex regulatory mechanisms.
