Nkx2.1-derived astrocytes and neurons together with Slit2 are indispensable for anterior commissure formation.

Shilpi Minocha,Alain Chédotal,Jean-Pierre Hornung,Oscar Marin,Elizabeth A. Allen,Yuchio Yanagawa,Athena R. Ypsilanti,Hubert Fiumelli,Delphine Valloton,Cécile Lebrand

doi:10.1038/ncomms7887

Abstract

Guidepost cells present at and surrounding the midline provide guidance cues that orient the growing axons through commissures. Here we show that the transcription factor Nkx2.1 known to control the specification of GABAergic interneurons also regulates the differentiation of astroglia and polydendrocytes within the mouse anterior commissure (AC). Nkx2.1-positive glia were found to originate from three germinal regions of the ventral telencephalon. Nkx2.1-derived glia were observed in and around the AC region by E14.5. Thereafter, a selective cell ablation strategy showed a synergistic role of Nkx2.1-derived cells, both GABAergic interneurons and astroglia, towards the proper formation of the AC. Finally, our results reveal that the Nkx2.1-regulated cells mediate AC axon guidance through the expression of the repellent cue, Slit2. These results bring forth interesting insights about the spatial and temporal origin of midline telencephalic glia, and highlight the importance of neurons and astroglia towards the formation of midline commissures.

Highlights

Guidepost cells present at and surrounding the midline provide guidance cues that orient the growing axons through commissures
We found numerous Nkx2.1 þ astrocytes in the anterior commissure (AC) white matter and in the tunnel region surrounding it from E14.5 to E18.5
They expressed markers such as Nestin, glutamate aspartate transporter (GLAST) and glial fibrillary acidic protein (GFAP) that are specific for postmitotic astrocytes in the AC (Fig. 1 and Supplementary Fig. 1a–c)

Summary

Introduction

Guidepost cells present at and surrounding the midline provide guidance cues that orient the growing axons through commissures. While confirming previous reports pointing towards a guidepost role for telencephalic glia, these results provide new insights for understanding the exact origin and function of these astrocytes in the axonal guidance of AC axons and the transcriptional regulation of these cells. This will give an additional insight on the genetic contribution and cellular mechanisms involved in abnormal commissural connections of the mammalian forebrain, including human patients

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