Elsevier

Developmental Biology

Volume 385, Issue 1, 1 January 2014, Pages 94-106
Developmental Biology

Ldb1 is essential for development of Nkx2.1 lineage derived GABAergic and cholinergic neurons in the telencephalon

https://doi.org/10.1016/j.ydbio.2013.10.010Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Ldb1 is expressed in the Nkx2.1lineage in the developing ventral telencephalon.

  • Ldb1 controls expression of a series of genes critical for telencephalon development.

  • Ldb1 regulates the tangential migration of ventral telencephalon derived neurons.

  • Ldb1 is essential for the generation of a variety of telencephalic neurons.

Abstract

The progenitor zones of the embryonic mouse ventral telencephalon give rise to GABAergic and cholinergic neurons. We have shown previously that two LIM-homeodomain (LIM-HD) transcription factors, Lhx6 and Lhx8, that are downstream of Nkx2.1, are critical for the development of telencephalic GABAergic and cholinergic neurons. Here we investigate the role of Ldb1, a nuclear protein that binds directly to all LIM-HD factors, in the development of these ventral telencephalon derived neurons. We show that Ldb1 is expressed in the Nkx2.1 cell lineage during embryonic development and in mature neurons. Conditional deletion of Ldb1 causes defects in the expression of a series of genes in the ventral telencephalon and severe impairment in the tangential migration of cortical interneurons from the ventral telencephalon. Similar to the phenotypes observed in Lhx6 or Lhx8 mutant mice, the Ldb1 conditional mutants show a reduction in the number of both GABAergic and cholinergic neurons in the telencephalon. Furthermore, our analysis reveals defects in the development of the parvalbumin-positive neurons in the globus pallidus and striatum of the Ldb1 mutants. These results provide evidence that Ldb1 plays an essential role as a transcription co-regulator of Lhx6 and Lhx8 in the control of mammalian telencephalon development.

Keywords

Differentiation
Forebrain development
Interneuron
Mouse
Tangential migration

Cited by (0)

1

Present address: Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.

2

Present address: Quanticel Pharmaceuticals, San Francisco, CA, USA.

3

Permanent address: Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Hungary.