The mammalian neocortex contains two major classes of neurons, projection and local circuit neurons. Projection neurons contain the excitatory neurotransmitter glutamate, while local circuit neurons are inhibitory, containing GABA. The complex function of neocortical circuitry depends on the number and diversity of GABAergic (γ-aminobutyric-acid-releasing) local circuit neurons. Using retroviral labelling in organotypic slice cultures of the embryonic human forebrain, we demonstrate the existence of two distinct lineages of neocortical GABAergic neurons. One lineage expresses Dlx1/2 and Mash1 transcription factors, represents 65% of neocortical GABAergic neurons in humans, and originates from Mash1-expressing progenitors of the neocortical ventricular and subventricular zone of the dorsal forebrain. The second lineage, characterized by the expression of Dlx1/2 but not Mash1, forms around 35% of the GABAergic neurons and originates from the ganglionic eminence of the ventral forebrain. We suggest that modifications in the expression pattern of transcription factors in the forebrain may underlie species-specific programmes for the generation of neocortical local circuit neurons5,6,7,8,9,10,11 and that distinct lineages of cortical interneurons may be differentially affected in genetic and acquired diseases of the human brain.
Limitation of this paper
from nowakowski paper intro
Short-term clonal labelling of progenitors in the human cortex revealed the local generation of newborn GABAergic neurons7 (cite this paper), but did not determine whether they were cortical interneurons or another type of interneuron such as those of the olfactory bulb, which have previously been shown to derive from cortical progenitors in mice11,12,13. Similarly, in vitro cultures derived from human cortical progenitors have been shown to generate GABAergic inhibitory neurons10.
