Parcellation of the striatal complex into dorsal and ventral districts

Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7418-7429. doi: 10.1073/pnas.1921007117. Epub 2020 Mar 13.


The striatal complex of basal ganglia comprises two functionally distinct districts. The dorsal district controls motor and cognitive functions. The ventral district regulates the limbic function of motivation, reward, and emotion. The dorsoventral parcellation of the striatum also is of clinical importance as differential striatal pathophysiologies occur in Huntington's disease, Parkinson's disease, and drug addiction disorders. Despite these striking neurobiologic contrasts, it is largely unknown how the dorsal and ventral divisions of the striatum are set up. Here, we demonstrate that interactions between the two key transcription factors Nolz-1 and Dlx1/2 control the migratory paths of striatal neurons to the dorsal or ventral striatum. Moreover, these same transcription factors control the cell identity of striatal projection neurons in both the dorsal and the ventral striata including the D1-direct and D2-indirect pathways. We show that Nolz-1, through the I12b enhancer, represses Dlx1/2, allowing normal migration of striatal neurons to dorsal and ventral locations. We demonstrate that deletion, up-regulation, and down-regulation of Nolz-1 and Dlx1/2 can produce a striatal phenotype characterized by a withered dorsal striatum and an enlarged ventral striatum and that we can rescue this phenotype by manipulating the interactions between Nolz-1 and Dlx1/2 transcription factors. Our study indicates that the two-tier system of striatal complex is built by coupling of cell-type identity and migration and suggests that the fundamental basis for divisions of the striatum known to be differentially vulnerable at maturity is already encoded by the time embryonic striatal neurons begin their migrations into developing striata.

Keywords: basal ganglia; dorsal striatum; nucleus accumbens; olfactory tubercle; ventral striatum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basal Ganglia / cytology*
  • Basal Ganglia / metabolism
  • Cell Differentiation
  • Corpus Striatum / cytology*
  • Corpus Striatum / metabolism
  • Female
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Interneurons / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Ventral Striatum / cytology*
  • Ventral Striatum / metabolism


  • Distal-less homeobox proteins
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Transcription Factors
  • Zfp503 protein, mouse