From Human Pluripotent Stem Cells to Cortical Circuits.

Understanding the development of the human brain in relation with evolution is an important frontier field in developmental biology. In particular, investigating the mechanisms underlying the greatly increased relative size and complexity of the cerebral cortex, the seat of our enhanced cognitive abilities, remains a fascinating yet largely unsolved question. Though many advances in our understanding have been gained from the study of animal models, as well as human genetics and embryology, large gaps remain in our knowledge of the molecular mechanisms that control human cortical development.

The assembly of developing motor neurons depends on an interplay between spontaneous activity, type II cadherins and gap junctions.

A core structural and functional motif of the vertebrate central nervous system is discrete clusters of neurons or 'nuclei'. Yet the developmental mechanisms underlying this fundamental mode of organisation are largely unknown. We have previously shown that the assembly of motor neurons into nuclei depends on cadherin-mediated adhesion.

Central topography of cranial motor nuclei controlled by differential cadherin expression.

Neuronal nuclei are prominent, evolutionarily conserved features of vertebrate central nervous system (CNS) organization. Nuclei are clusters of soma of functionally related neurons and are located in highly stereotyped positions. Establishment of this CNS topography is critical to neural circuit assembly.