Gene regulation organises the spinal cord

04 October 2013

Research by scientists from NIMR has provided new insight into how different regions of the spinal cord emerge during embryonic development. The work is published in PLOS Genetics.

Many tissues are organised in complicated but highly structured ways. This ensures that cells with different tasks reside in appropriate locations and enables the proper function of tissues. The organisation of a tissue is established during embryonic development and involves an interplay between secreted signals received by cells and intracellular transcription factors, which control gene activity. This results in spatial patterns of gene activity in the forming tissue that delineate precursors for specific types of cells.

In this study, Steve Moore and colleagues from the laboratory of James Briscoe (pictured) scrutinise the formation of precursors of different nerve cells in the spinal cord. In this tissue nerve cells that process sensory information are distinct from those that control motor function and the two types reside in different locations. To gain insight into the molecular mechanisms by which the spinal cord is segregated into these two functional regions, the team identified and analysed the parts of the genome responsible for regulating the production of a transcription factor, Pax3, which is specifically active in sensory precursors. They identified two genomic regions that act in a coordinated way to integrate the activity of the signals and transcription factors and thereby establish and maintain Pax3 activity.

We showed that the combination of activating signals from secreted Wnt factors together with Nkx family transcription factors restrict Pax3 activity to the presumptive sensory region of the spinal cord. Subsequently, Pax3 acts to directly potentiate its own expression and this autoregulation sustains Pax3 at later developmental stages. This reveals how a combination of intrinsic and extrinsic signals are integrated by cells and converted into a sustained pattern of gene activity in the developing nervous system.

Vanessa Ribes

Click image to view at full-size

Analysis of Pax3 regulation in the CNS. A reporter from a genomic region of the Pax3 gene (white/green) recapitulates the activity of the endogenous Pax3 gene (red) in the zebrafish spinal cord (dotted outline).

Original article

Moore S, Ribes V, Terriente J, Wilkinson D, Relaix F, and Briscoe, J. (2013)

Distinct regulatory mechanisms act to establish and maintain Pax3 expression in the developing neural tube.

PLOS Genetics 9(10): e1003811. Article fulltext.

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