Modular patterning of structure and function of the striatum by retinoid receptor signaling

Wen Lin Liao, Hsiu Chao Tsai, Hsiao Fang Wang, Josephine Chang, Kuan Ming Lu, Hsiao Lin Wu, Yi Chao Lee, Ting Fen Tsai, Hiroshi Takahashi, Michael Wagner, Norbert B. Ghyselinck, Pierre Chambon, Fu Chin Liu

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Retinoid signaling plays a crucial role in patterning rhombomeres in the hindbrain and motor neurons in the spinal cord during development. A fundamentally interesting question is whether retinoids can pattern functional organization in the forebrain that generates a high order of cognitive behavior. The striatum contains a compartmental structure of striosome (or "patch") and intervening matrix. How this highly complex mosaic design is patterned by the genetic programs during development remains elusive. We report a developmental mechanism by which retinoid receptor signaling controls compartmental formation in the striatum. We analyzed RARβ-/- mutant mice and found a selective loss of striosomal compartmentalization in the rostral mutant striatum. The loss of RARβ signaling in the mutant mice resulted in reduction of cyclin E2, a cell cycle protein regulating transition from G1 to S phase, and also reduction of the proneural gene Mash1, which led to defective neurogenesis of late-born striosomal cells. Importantly, during striatal neurogenesis, endogenous levels of retinoic acid were spatiotemporally regulated such that transduction of high levels of retinoic acid through RARβ selectively expanded the population of late-born striosomal progenitors, which evolved into a highly elaborate compartment in the rostral striatum. RARβ-/- mutant mice, which lacked such enlarged compartment, displayed complex alternations of dopamine agonist-induced stereotypic motor behavior, including exaggeration of head bobbing movement and reduction of rearing activity. RARβ signaling thus plays a crucial role in setting up striatal compartments that may engage in neural circuits of psychomotor control.

Original languageEnglish
Pages (from-to)6765-6770
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number18
DOIs
Publication statusPublished - May 6 2008
Externally publishedYes

Keywords

  • Basal ganglia
  • Cell proliferation
  • Retinoic acid
  • Stereotypic behavior

ASJC Scopus subject areas

  • Genetics
  • General

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  • Cite this

    Liao, W. L., Tsai, H. C., Wang, H. F., Chang, J., Lu, K. M., Wu, H. L., Lee, Y. C., Tsai, T. F., Takahashi, H., Wagner, M., Ghyselinck, N. B., Chambon, P., & Liu, F. C. (2008). Modular patterning of structure and function of the striatum by retinoid receptor signaling. Proceedings of the National Academy of Sciences of the United States of America, 105(18), 6765-6770. https://doi.org/10.1073/pnas.0802109105