Research in the Kessaris Lab

We study neuronal development from embryonic and adult neural stem cells focusing on neuronal subtypes generated from subpallial precursors in the embryo and subventricular zone stem cells in the adult brain. We examine the genetic basis of neuronal subtype specification, migration, differentiation and circuit integration. We use genetic manipulation in mice to fate-map precursor cells, tag and purify stem cells and their progeny in order to identify genes involved in their development. We manipulate gene function using loss- and gain-of-function approaches. We are also developing genetic tools to trace neuronal connections in vivo and manipulate neuronal activity in order to examine participation in neuronal circuits.

Cortical Interneuron Development

Interneurons in the adult cortex represent a heterogeneous population of cells in terms of morphology, neurochemical and physiological properties. It is unknown how this diversity arises, what the significance of the diversity is and what the function of these interneuron subtypes might be in cortical circuits. We believe that interneuron diversity is specified to a large extent during embryogenesis and that functionally related groups of cells may be generated form common precursors. Using genetic fate-mapping approaches we label molecularly distinct precursor cells and identify neuronal progeny. This will not only enable us to identify the embryonic origins of these cells but will also provide us with tools to further manipulate their function. Unlike projection neurons of the cortex which are generated from resident cortical precursors, interneurons are generated form distant neuroepithelial stem cells in the ventral telencephalon and migrate long distances to reach the cortex. We examine the molecular basis of interneuron navigation through the basal forebrain, migration into the cortex and integration into functional circuits.

Forebrain Neurogenesis

The two major germinal zones of the telencephalon (the medial and lateral ganglionic eminences MGE and LGE, respectively) generate a large spectrum of interneurons and principal neurons including neurons of the basal ganglia such as the pallidum and striatum. Whether MGE-derived neurons for example originate from common precursors or spatially segregated cells is unknown. Three major players involved in cell fate choices in the medial ganglionic eminence are the homeobox transcription factors Nkx2.1, Lhx6 and Lhx7. Using genetic manipulations we examine the role of these and other factors implicated in early aspects of neuronal development from resident precursor cells.

Olfactory Bulb Neurogenesis From Embryonic And Adult Neural Stem Cells

Unlike most other regions of the brain where neurogenesis ceases at early postnatal stages, the olfactory bulb is supplied with new neurons throughout life. We are only beginning to understand this process and the significance it has on olfaction. Our work aims to examine neuronal development in the olfactory bulb. We study the embryonic origins of olfactory bulb neurons from embryonic and adult neural stem cells using a combination of genetic approaches. We aim to understand how neuronal diversity arises in the olfactory bulb, the molecular basis of interneuron specification from adult neural stem cells and how these cells navigate through the adult brain to reach their distant targets in the olfactory bulb. This work will provide us with basic knowledge into olfactory bulb circuit assembly. Understanding how adult neural stem cells generate distinct neuronal subtypes under normal conditions will also provide us with clues as to how we might be able to stimulate neural stem cells to respond to injury and steer their fate towards particular cell types.

Last updated 11 Oct 08