Does cell lineage in the developing cerebral cortex contribute to its columnar organization?

Abstract

Since the pioneer work of Lorente de Nó, Ramón y Cajal, Brodmann, Mountcastle, Hubel and Wiesel and others, the cerebral cortex has been seen as a jigsaw of anatomic and functional modules involved in the processing of different sets of information. In fact, a columnar distribution of neurons displaying similar functional properties throughout the cerebral cortex has been observed by many researchers. Although it has been suggested that much of the anatomical substrate for such organization would be already specified at early developmental stages, before activity-dependent mechanisms could take place, it is still unclear whether gene expression in the ventricular zone (VZ) could play a role in the development of discrete functional units, such as minicolumns or columns. Cell lineage experiments using replication-incompetent retroviral vectors have shown that the progeny of a single neuroepithelial/radial glial cell in the dorsal telencephalon is organized into discrete radial clusters of sibling excitatory neurons, which have a higher propensity for developing chemical synapses with each other rather than with neighboring non-siblings. Here, we will discuss the possibility that the cell lineage of single neuroepithelial/radial glia cells could contribute for the columnar organization of the neocortex by generating radial columns of sibling, interconnected neurons. Borrowing some concepts from the studies on cell-cell recognition and transcription factor networks, we will also touch upon the potential molecular mechanisms involved in the establishment of sibling-neuron circuits.

Keywords: cell lineage; cortical columns; sister neurons; transcription factors.

Figure 1

Columnar distribution of sister neurons in the cerebral cortex. (A) Schematic representation of a single progenitor cell transfected by a retroviral vector and its subsequent progeny (green). (B) Coronal section of the adult mouse cerebral cortex labeled for GFP (green) and DAPI (blue) where two neuronal siblings can be observed. For this experiment, the retrovirus carrying the gene for the protein GFP was injected into the lateral ventricle of an E13 animal. Abbreviations: VZ, ventricular zone; CAG-GFP, green fluorescent protein encoding plasmid; L, layer. Calibration bar: 100 μm.

Figure 2

Hypothetic model for the generation of functional units from individual progenitors. Schematic drawing showing three progenitor cells in the embryonic ventricular zone (VZ) expressing different sets/levels of transcription factors, labeled in red, blue, and green. Each of these cells generates a clone of pyramidal neurons that inherit analogous genetic information from the founder progenitor and are organized in discrete radial arrays in the adult cerebral cortex. The similar genetic pedigree of sibling neurons allows their recognition and establishment of synaptic connections, creating a microcircuit of clonally related glutamatergic neurons.