Loss of <i>Nkx2.1</i> homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum

TLDR

The telencephalon is divided into the cerebral cortex and basal ganglia, with the basal ganglia comprising a dorsal striatum and ventral pallidum that originates from Nkx2.1‑expressing progenitors; loss of Nkx2.1 disrupts pallidal development, reduces basal forebrain cholinergic neurons, and diminishes GABAergic cortical interneurons derived from the pallidum. The study aims to demonstrate that loss of Nkx2.1 causes a ventral‑to‑dorsal transformation of the pallidal primordium into a striatal‑like anlage. The data reveal that this transformation accounts for the observed phenotypes.

Abstract

Abstract The telencephalon is organized into distinct longitudinal domains: the cerebral cortex and the basal ganglia. The basal ganglia primarily consists of a dorsal region (striatum) and a ventral region (pallidum). Within the telencephalon, the anlage of the pallidum expresses the Nkx2.1 homeobox gene. A mouse deficient in Nkx2.1 function does not form pallidal structures, lacks basal forebrain TrkA-positive neurons (probable cholinergic neurons) and has reduced numbers of cortical cells expressing GABA, DLX2 and calbindin that migrate from the pallidum through the striatum and into the cortex. We present evidence that these phenotypes result from a ventral-to-dorsal transformation of the pallidal primordium into a striatal-like anlage.