Migration And Differentiation Of Enteric Neuron Precursors
Funder
National Health and Medical Research Council
Funding Amount
$385,116.00
Summary
There are many 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 ....There are many 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 small and large intestines by neural crest cells takes over 4 days, and in humans the process probably takes at least one week. It is essential that the 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. It is therefore essential that migratory neural crest cells colonise the entire gastrointestinal tract. Currently, little is known about the mechanisms controlling the migration of neural crest cells, and whether a) particular molecules within the gut wall are important for migration, and-or b) the migratory behaviour of the neural crest cells is regulated mostly by the neural crest cells themselves. In this study we will take time-lapse images of neural crest cells migrating through the gut of embryonic mice to identify the factors that are important for the migration. After the neural crest cells have colonised the entire intestine, they develop into different types of nerve cells. We will also examine some of the factors affecting the development of different types of nerve cells.Read moreRead less
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
Central pathways regulating visceral pain. This project aims to investigate the neural pathways within the spinal cord and brain processing colorectal pain perception. The project aims to identify the spinal cord neurons relaying colorectal signalling into the brain and the influence of descending modulation from the brainstem upon these pathways. The outcomes will greatly benefit fundamental understanding of the central pathways processing visceral pain.
Psychiatric disorders in epilepsy. Psychiatric disorders, such as depression, anxiety and cognitive disorders, are frequently observed in patients with epilepsy. Although standard dogma suggests that psychiatric disorders are a consequence of living with epilepsy, recent evidence suggests a bidirectional relationship between these disorders, such that depression and other psychiatric illnesses act as risk factors for epilepsy development. This project will utilise basic science approaches to und ....Psychiatric disorders in epilepsy. Psychiatric disorders, such as depression, anxiety and cognitive disorders, are frequently observed in patients with epilepsy. Although standard dogma suggests that psychiatric disorders are a consequence of living with epilepsy, recent evidence suggests a bidirectional relationship between these disorders, such that depression and other psychiatric illnesses act as risk factors for epilepsy development. This project will utilise basic science approaches to understand the causal relationships between epilepsy and psychiatric disorders, and determine how and why psychiatric disorders and epilepsy co-exist. It is hoped that research conducted in this project will develop novel avenues to treatment of both epilepsy and psychiatric disorders.Read moreRead less
UNDERSTANDING THE BASIS OF COMPLEX BEHAVIOUR. This project is anchored in the fundamental understanding of complex vertebrate behaviours, namely cognition. Little is known about the molecular and neural substrates underpinning complex higher order information processing. This project aims to dissect the functional role of synaptic genes that are essential for organising neuronal connections, in distinct cognitive processes and how these functions may be regulated by other genes, drugs or environ ....UNDERSTANDING THE BASIS OF COMPLEX BEHAVIOUR. This project is anchored in the fundamental understanding of complex vertebrate behaviours, namely cognition. Little is known about the molecular and neural substrates underpinning complex higher order information processing. This project aims to dissect the functional role of synaptic genes that are essential for organising neuronal connections, in distinct cognitive processes and how these functions may be regulated by other genes, drugs or environmental factors. This project aims to employ state-of-the-art technologies to address the evolutionary biology of complex cognitive behaviours, towards further understandings how brain function evolved and the mechanisms that have enabled humans to perform highly complex and intricate tasks.Read moreRead less
Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also mi ....Neural migration: Which cells advance and which stay behind? This project aims to examine the neural crest cells that colonise the developing gut and to identify why some cells advance while others stay behind to populate a region. Directed cell migration is essential for normal development, including for the nervous system. In most of the migratory cell populations that have been analysed to date, all of the cells migrate as a collective from one location to another. However, there are also migratory cell populations that must populate the areas through which they migrate, and thus some cells get left behind while others advance. The planned data are likely to be relevant to other cell populations that also populate the areas through which they migrate, including neural crest-derived melanocytes and Schwann cell precursors.Read moreRead less
How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information i ....How the brain regulates blood pressure. This project will test whether a group of nerve cells in the rostral ventrolateral medulla generate sympathetic activity in blood vessels. The brain regulates blood pressure through several pathways, including nerves in the sympathetic nervous system that constrict blood vessels and increase the heart rate. Activity of these sympathetic nerves regulates blood pressure, but it is unknown which nerve cells in the brain cause this activity. This information is essential to understand how blood pressure is controlled under healthy conditions.Read moreRead less
The jugular vagal sensory connectome regulating visceral function. Internal body organs have a rich supply of sensory nerve fibres that serve important roles in monitoring the local environment for normal and abnormal sensory stimuli. These nerve fibres have different origins and wire into brain circuits that regulate widely diverse physiological responses. In this study we aim to study the neural circuits and responses mediated by a group of these sensory nerves which has not been investigated ....The jugular vagal sensory connectome regulating visceral function. Internal body organs have a rich supply of sensory nerve fibres that serve important roles in monitoring the local environment for normal and abnormal sensory stimuli. These nerve fibres have different origins and wire into brain circuits that regulate widely diverse physiological responses. In this study we aim to study the neural circuits and responses mediated by a group of these sensory nerves which has not been investigated appreciably in the past. We believe that these sensory neural circuits will reveal important new insights into how internal organs perform their diverse and essential functions to sustain life.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE230101079
Funder
Australian Research Council
Funding Amount
$453,528.00
Summary
New insights into how the brain interprets visceral and somatic sensations. Sensory nerve fibres monitor normal and abnormal stimuli in our body tissues, sending this information to the brain. I study the sensory pathways of the respiratory system which protect the lungs from harmful stimuli, such as inhaled pollutants or smoke. I discovered that respiratory sensory pathways interact with sensory circuits in the brain arising from other body tissues. The goal of this project is to investigate on ....New insights into how the brain interprets visceral and somatic sensations. Sensory nerve fibres monitor normal and abnormal stimuli in our body tissues, sending this information to the brain. I study the sensory pathways of the respiratory system which protect the lungs from harmful stimuli, such as inhaled pollutants or smoke. I discovered that respiratory sensory pathways interact with sensory circuits in the brain arising from other body tissues. The goal of this project is to investigate one example of this interaction; the convergence of visceral and somatic sensory pathways onto a brain circuit that regulates the intensity of the sensations that are experienced. This project addresses the fundamental question of how the brain processes two competing noxious sensations.Read moreRead less
Discovery Early Career Researcher Award - Grant ID: DE130100323
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
The regulation by transcription factor phosphorylation upon the myelinating process. The project will investigate the novel molecular events that control the myelinating process, which is essential for normal nervous system function. Outcomes of this project may aid the development of novel interventions to improve control of demyelinating diseases, which represent a substantial socio-economic burden.