Cellular Mechanisms Controlling Neural Crest Cell Migration Along The Developing Gut
Funder
National Health and Medical Research Council
Funding Amount
$368,895.00
Summary
Within the wall of the gut, there are a large number of neurons, probably more than are in the spinal cord. These enteric neurons play an essential role in controlling a number of gut functions including peristalsis (the propulsion of contents along the gut). Most of the neurons in the gut, including those in the large intestine, arise from precursors that emigrate from the hindbrain, and then migrate into and along the gastrointestinal tract during development. The colonization of the gut by ne ....Within the wall of the gut, there are a large number of neurons, probably more than are in the spinal cord. These enteric neurons play an essential role in controlling a number of gut functions including peristalsis (the propulsion of contents along the gut). Most of the neurons in the gut, including those in the large intestine, arise from precursors that emigrate from the hindbrain, and then migrate into and along the gastrointestinal tract during development. The colonization of the gut by neuron precursors takes 5 days in mice and 6 weeks in humans. Studies of the mechanisms controlling the migration of neuron precursors along the gut have provided fundamental information about cell migration in general. Genetic studies in humans and mice have identified some of the genes that are necessary for the migration of neuron precursors along the gastrointestinal tract, but for some of the key genes, their precise role is unknown. We have recently developed a method for imaging living neuron precursors migrating through explants of embryonic mouse gut. In the current proposal we will meld imaging and genetic studies to understand how mutations in particular genes lead to migration defects. In particular, how do particular mutations affect the migratory behaviour of enteric neural precursors? We have also previously shown that neuron precursors migrate along the gut in close association with axons. We will examine the nature of these interactions - in particular, who is following whom, and what happens when cell migration and axon growth are uncoupled? These studies, which will investigate a number of critical aspects of the migration of neural precursors into and along the developing gut, are central to understanding how the enteric nervous system is established along the gastrointestinal tract.Read moreRead less
The Importance Of Superstars: Cell Numbers And Lineages In Enteric Nervous System Formation
Funder
National Health and Medical Research Council
Funding Amount
$561,717.00
Summary
All digestive functions are controlled by a nerve system in the gut wall, and it works without us thinking about it. This is a huge system rivalling the spinal cord in number of nerve cells. And it has may different types of nerve cells. It originates from a very few cells early in the embryo, about 200 times fewer than the spinal cord. How do the cells manage to divide enough to make this system, and how do they 'know' how to make the right types of nerve cells in the right places in the gut?
Gut motility requires enteric neurons, which are located in the gut wall. During development, enteric neurons arise from precursors in the brain that migrate into the intestine. Failure of enteric neuron precursors to migrate and differentiate normally results in pediatric motility disorders. The aim of this research is to identify the mechanisms controlling the development of enteric neurons so that therapies can be developed for pediatric motility disorders.
Guidance Molecules Involved In The Development Of The Enteric Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$369,250.00
Summary
There are millions of nerve cells within the wall of the intestine, and they control many intestinal functions, including motility. During development, these nerve cells arise from cells which migrate away from the developing brain and first enter the stomach. The migratory cells are called 'neural crest' cells. After entering the stomach, neural crest cells migrate within the wall of the gastrointestinal tract, until they reach the far (anal) end. In embryonic mice, this colonisation of the ent ....There are millions of nerve cells within the wall of the intestine, and they control many intestinal functions, including motility. During development, these nerve cells arise from cells which migrate away from the developing brain and first enter the stomach. The migratory cells are called 'neural crest' cells. After entering the stomach, neural crest cells migrate within the wall of the gastrointestinal tract, until they reach the far (anal) end. In embryonic mice, this colonisation of the entire gut by neural crest cells takes over four days, and in humans the process probably takes around three weeks. It is essential that neural crest cells colonise the entire gastrointestinal tract, since regions of intestine lacking neural crest cells (and hence nerve cells) cannot function and intestinal contents build up in front of the region lacking nerve cells. This condition is found in some babies (Hirschsprung's disease), and it can only be treated by surgically removing the region lacking nerve cells. Currently, little is known about the mechanisms controlling the migration of neural crest cells within the gut, and whether particular molecules are involved in this process. In this study, we will use a variety of methods to identify the molecules that are involved in the migration of neural crest cells into and along the developing gut.Read moreRead less