Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Mar 8:12:1179069518760783.
doi: 10.1177/1179069518760783. eCollection 2018.

Single-Cell Transcriptomics Reveals Regulators of Neuronal Migration and Maturation During Brain Development

Daniel Pensold  1 , Geraldine Zimmer  1
Affiliations

Single-Cell Transcriptomics Reveals Regulators of Neuronal Migration and Maturation During Brain Development

Daniel Pensold et al. J Exp Neurosci. .

Abstract

The correct establishment of inhibitory circuits is crucial for cortical functionality and defects during the development of γ-aminobutyric acid-expressing cortical interneurons contribute to the pathophysiology of psychiatric disorders. A critical developmental step is the migration of cortical interneurons from their site of origin within the subpallium to the cerebral cortex, orchestrated by intrinsic and extrinsic signals. In addition to genetic networks, epigenetic mechanisms such as DNA methylation by DNA methyltransferases (DNMTs) are suggested to drive stage-specific gene expression underlying developmental processes. The mosaic structure of the interneuron generating domains producing a variety of interneurons for diverse destinations complicates research on regulatory instances of cortical interneuron migration. To this end, we performed single-cell transcriptome analysis revealing Dnmt1 expression in subsets of migrating interneurons. We found that DNMT1 preserves the migratory morphology in part through transcriptional control over Pak6 that promotes neurite complexity in postmigratory cells. In addition, we identified Ccdc184, a gene of unknown function, to be highly expressed in postmitotic interneurons. Single-cell mRNA sequencing revealed a positive correlation of Ccdc184 with cell adhesion-associated genes pointing to potential implications of CCDC184 in processes relying on cell-cell adhesion-like migration or morphological differentiation of interneurons that deserves further investigations.

Keywords: Ccdc184; DNMT; Pak6; Single-cell transcriptomics; epigenetics; interneurons; maturation; migration.

PubMed Disclaimer

Conflict of interest statement

Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Ccdc184 is associated with cadherin-based cell-cell adhesion processes in POA-derived interneurons. (A) In situ hybridization against Ccdc184 in E14.5 sagittal sections of C57/Bl6 mice shows expression in the ventral part of the basal telencephalon and especially in the preoptic area (POA). (B) The methylation density of the Ccdc184 locus is not reduced in Dnmt1-deficient Hmx3-Cre/tdTomato cells compared to wild-type as revealed by MeDIP (methylated DNA immunoprecipitation) sequencing. (C, D) Gene Ontology (GO) enrichment analysis of genes found significantly correlated with Ccdc184 (R > 0.7 in C) in POA-derived single cells revealed an enrichment of cell-cell adhesion–associated genes. Further terms related to RNA processing and gene expression appear when expanding the correlated genes to a correlation coefficient of (D) R > 0.5. (E-G) In situ hybridization against (E) Cdh8, (F) Pcdh9, and (G) Celsr2 in E14.5 sagittal sections of C57/Bl6 mice showing expression of these cadherins in the POA. In situ hybridizations were obtained from Gene Expression Database (GXD) or genepaint.org; accession numbers are provided in each panel. Data analysis was performed as described in the work by Pensold et al., 2017.
See this image and copyright information in PMC

Comment on

  • J Exp Neurosci. 27:5696.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Marin O. Cellular and molecular mechanisms controlling the migration of neocortical interneurons. Eur J Neurosci. 2013;38:2019–2029. - PubMed
    1. Marin O. Interneuron dysfunction in psychiatric disorders. Nat Rev Neurosci. 2012;13:107–120. - PubMed
    1. Lopez-Bendito G, Arlotta P. Cell replacement therapies for nervous system regeneration. Develop Neurobiol. 2012;72:145–152. - PMC - PubMed
    1. Antypa M, Faux C, Eichele G, Parnavelas JG, Andrews WD. Differential gene expression in migratory streams of cortical interneurons. Eur J Neurosci. 2011;34:1584–1594. - PMC - PubMed
    1. Zimmer G, Rudolph J, Landmann J, et al. Bidirectional ephrinB3/EphA4 signaling mediates the segregation of medial ganglionic eminence- and preoptic area-derived interneurons in the deep and superficial migratory stream. J Neurosci Met. 2011;31:18364–18380. - PMC - PubMed

LinkOut - more resources