Differentiation And Fate In The Developing Sympathetic Ganglia
Funder
National Health and Medical Research Council
Funding Amount
$353,754.00
Summary
This project seeks to understand how a small number of founder cells can divide and differentiate into the myriad different types of cells that make up the mature nervous system. It uses modern genetic techniques to follow progenitor cells as they mature into mature neurons.
Role Of Kinesin Binding Protein And Spontaneous Activity In The Development Of Enteric Neurons
Funder
National Health and Medical Research Council
Funding Amount
$599,889.00
Summary
The nerve cells in the wall of the gut play an essential role in motility. Defects in the development of these nerve cells results in pediatric motility disorders. We will examine the roles of two factors, kinesin binding protein, and spontaneous activity in the development of enteric neurons.
Role Of Microbiota In The Developing Enteric Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$661,979.00
Summary
The correct development of neurons in the gut is vital for digestive functions. This project will provide novel insights into how environmental factors such as the bacteria that reside in the gut and changes in diet affect maturation of the gut’s nervous system. The data will improve knowledge of the effects of widely used antibiotics and probiotics, which will facilitate strategies to improve human health and quality of life.
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?
Cell Therapy For Enteric Neuropathies - The Essential Next Steps
Funder
National Health and Medical Research Council
Funding Amount
$667,142.00
Summary
Gastrointestinal motility disorders caused by damage or diseased neurons in the gut wall ("enteric neuropathies) are some of the most clinically challenging conditions to manage because of a lack of effective treatments. Our recent animal studies suggest that cell-based therapies are a real possibility to treat enteric neuropathies. In this project, we will methodically address the outstanding steps that need to be addressed with the aim of moving enteric cell therapies to the clinic.
Neurons within the wall of the bowel play an essential role in gut motility. A number of motility disorders are caused by diseased enteric neurons, but there are currently no effective treatments for these diseases. We will use animal models of a pediatric motility disorder to examine whether stem cells implanted into the colon can generate neurons and restore normal motility.
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
Neural Circuits Producing Pelvic Vasodilation In Females
Funder
National Health and Medical Research Council
Funding Amount
$472,770.00
Summary
The reproductive organs and genitalia in males and females experience a large increase in blood flow during sexual and reproductive activity. This increased blood flow (vasodilation) is a key component of penile and clitoral erection, and enhances secretion from the lining of the internal reproductive organs. Vasodilation during sexual activity is produced by a special sets of nerves receiving signals from the genitalia and the brain. In fact, Viagra works by enhancing and prolonging the actions ....The reproductive organs and genitalia in males and females experience a large increase in blood flow during sexual and reproductive activity. This increased blood flow (vasodilation) is a key component of penile and clitoral erection, and enhances secretion from the lining of the internal reproductive organs. Vasodilation during sexual activity is produced by a special sets of nerves receiving signals from the genitalia and the brain. In fact, Viagra works by enhancing and prolonging the actions of these nerves. An important part of this neural pathway is a group of nerve cells in the spinal cord that connects the central nervous system with peripheral nerves in the reproductive organs - these are called preganglionic neurons. Recently we discovered that a major pathway from the spinal cord to the pelvic blood vessels in females leaves the spinal cord at a different level (lumbar) from that thought previously (sacral level). Currently there is no information on how these lumbar preganglionic nerves in females are connected to other nerve pathways that are active during sexual activity, and how they integrate signals from both the internal organs and the brain. We will use an array of modern cellular techniques together with direct observation of dilation in isolated uterine arteries to discover how these nerve cells are wired up in circuits in the spinal cord. This information is vital for us to understand the factors producing increased blood flow in normal sexual activity, and how these might be altered in inflammation or in conditions where there could be selective damage to one nerve pathway and not the other, such as after pelvic surgery, spinal cord damage at different levels, or stimulation of the spinal cord for treatment of chronic pain. Our study also will help understand referred pain and sensations of discomfort in abdominal and pelvic organs.Read moreRead less
In this grant we will take advantage of procedures uniquely available to the applicant to identify the cell type from which the most prevalent extra cranial solid tumour in children, neuroblastoma (NB), arises during embryonic development. Further studies on this specific cell type will identify the factors controlling their correct embryonic development. Assessment of these molecules as therapeutic targets will then identify novel treatments to inhibit disease progression.
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