MCAHBC

Molecular and cellular analysis of hindbrain boundary cells

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 Obiettivo del progetto (Objective)

'The Central Nervous System (CNS) is divided in different compartment structures: Forebrain, Midbrain and Hindbrain. The hindbrain in turn is subdivided in rhombomeres: compartmental structures separated by boundaries. It has been described that another CNS compartment borders are organizing centres, but it’s unknown if the hindbrain boundaries have this role and which are the molecular mechanisms that specify this territory, to be distinguished from the remaining hindbrain cells. Nevertheless, there are cues that suggest that hindbrain boundaries act like organizing centres: Activation of signalling pathways and stereotypic organization of neuronal groups. Our questions are: (i) What are the mechanisms that induce boundary cells at the segment interfaces? (ii) What is the behaviour and fate of boundary cells? And, (iii) What is the role of boundaries in the zebrafish hindbrain? To answer them we’ll map the regulatory region of rfng, a hindbrain boundary marker, in order to know the region that drives its expression only in boundaries. Through this approach we follow two objectives: (1) To know which genes regulate its expression, and (2) to obtain transgenic lines, which express reporters in boundaries. These tools will help us, through the use of time-lapse microscopy and hystochemistry to address the boundary cell fate, proliferation, and gene expression. Both approaches will help us to understand the regulatory complex that drives the boundary specification and differentiation and also to know if: the rhombomere boundaries act like organizing centres.'

Introduzione (Teaser)

An EU-funded project has just completed research on how the hindbrain works. The work promises to shed light on the control of vital, yet unconscious body functions like breathing and swallowing.

Descrizione progetto (Article)

The brain is divided into three major areas: the 'civilised' forebrain, and the more 'primitive' midbrain and hindbrain. Aspects of control of the hindbrain have so far remained uncertain, but the work of the 'Molecular and cellular analysis of hindbrain boundary cells' (MCAHBC) project has helped to fill in some of the gaps.

Each section of the brain is divided into compartments, each being surrounded by so-called boundary cells. Previous work has shown that cells at the boundaries of brain compartments in certain regions play a large part in organisation. Researchers investigated whether boundary cells around compartments of the hindbrain also have a role in control.

Using the zebrafish model, project workers researched the formation as well as behaviour, fate and role of boundary cells in the hindbrain. Using genomic techniques, they mapped a stretch of genetic material, rfng, known to be involved in regulation.

The team used a combination of cell response to chemical staining, histochemistry, and time-lapse microscopy to unravel the gene control mechanisms. Moreover, the studies were designed to identify what genes were responsible for stem cells (undifferentiated cells) in the area becoming boundary cells and then being able to divide and proliferate.

The results give a promising insight into nervous system control. Interesting cross-talk or interaction was identified in the key signalling pathway known as Eph. This pathway is very important generally in most animals and is even implicated in the development of some cancers.

The significance of this research promises to be very diverse. Stem cell research is cutting edge and it appears that hindbrain boundary cells are an appropriate biological model to study stem cell dynamics and differentiation in central nervous system development.