The vertebrate central nervous system (CNS) consists of thousands of distinct neuronal cells, each with unique molecular genetic profiles, organised into complex patterns of circuitry that prefigure appropriate functional output. A key goal of modern developmental neuroscience is to unravel the molecular logic that first establishes the diversity in neuronal cell type and subsequently dictates their development into integrated higher order networks. Recent years have seen considerable progress in establishing the initial framework that underpins the acquisition of neuronal identity. Several lines of evidence have shown that cells are specified in discrete steps within the neuroepithelium influenced by the anteroposterior (AP) and dorsoventral (DV) position of precursor cell. In general, in response to a range of diffusible biochemical cues a series of 'high level' patterning cues or 'selector' genes (e.g. homeodomain transcription factors) establish the first molecular co-ordinates that imprint progenitor cells with an outline fate. However, despite this being well-recognised and investigates paradigm, we still remain relatively ignorant of the repertoire of subsequent molecular 'effectors' then impart specific facets of neuronal behaviour and connectivity. The developing vertebrate hindbrain and the adjacent signalling centre provide the ideal accessible system in which to examine the molecular controls underpinning the emergence of neuronal diversity. Exploiting the relationship between early anatomical distinctions and key selector gene activities of these territories we have generated fully representative and validated genome-wide expression libraries for each division of the hindbrain and the caudal portion of the midbrain. We use this data to investigate how neuronal specificity is achieved by the recruitment of effector genes and address the following questions;

What and how are the developmental genetic factors used in response the patterning influences of the mid-hindbrain signalling centre?

How do Hox genes drive downstream networks of effector gene activity?

Can we use this information to drive the differentiation of embryonic-derived stem cells towards specific fates?

A more complete understanding of the molecular logic of neuronal specification and how patterning instructions are relayed to a defined set of cellular cues is a prerequisite to expanding our knowledge of nervous system function in health and dysfunction. Furthermore, the genetic networks and effectors uncovered here will broadly impact on the more fundamental question of how a cell becomes ultimately specified during development and offers insights into the genetic basis of disease