Neogenin: A Regulator Of Neuronal Differentiation And Migration In The Adult Brain
Funder
National Health and Medical Research Council
Funding Amount
$334,053.00
Summary
Conditions such as Alzheimer�s and Huntington�s diseases, as well as stroke, represent a major burden of disease in Australia. One goal of modern neurobiology is to harness the brain's ability to make new neurons so that we can replace those damaged by disease or injury. We will investigate how an important developmental molecule, Neogenin, promotes the production of new neurons in the adult brain. A second goal is to show that Neogenin can be activated to promote the repair of the damaged brain ....Conditions such as Alzheimer�s and Huntington�s diseases, as well as stroke, represent a major burden of disease in Australia. One goal of modern neurobiology is to harness the brain's ability to make new neurons so that we can replace those damaged by disease or injury. We will investigate how an important developmental molecule, Neogenin, promotes the production of new neurons in the adult brain. A second goal is to show that Neogenin can be activated to promote the repair of the damaged brain.Read moreRead less
The Development Of Glial Cells In The Sympathetic Nervous System
Funder
National Health and Medical Research Council
Funding Amount
$372,025.00
Summary
Nervous system development entails the co-ordinated multiplication of a small number of founder cells to give the millions of cells of the mature nervous system. Each founder generates a many different cell types. Understanding how this is controlled is among the most challenging problems in modern biology. We will show how the development of the two basic cell types (neurons and glia), is controlled in a part of the nervous system that is relatively simple and accessible for manipulation.
Identification Of Genes Involved In Neural Crest Development
Funder
National Health and Medical Research Council
Funding Amount
$482,310.00
Summary
Knowledge of the genes that during embryonic development control the way our bodies form is necessary to understanding how our body systems function in health and disease. However, research on the developmental genetics of vertebrates, including humans, has proceeded very indirectly, mostly by looking for genes similar to those found in other biological systems, most notably the fruit fly. The significance of this research is that it will identify developmental genes directly from the chosen ver ....Knowledge of the genes that during embryonic development control the way our bodies form is necessary to understanding how our body systems function in health and disease. However, research on the developmental genetics of vertebrates, including humans, has proceeded very indirectly, mostly by looking for genes similar to those found in other biological systems, most notably the fruit fly. The significance of this research is that it will identify developmental genes directly from the chosen vertebrate body system as it develops. As a body system we will choose one of the most basic building blocks of the very early nervous system. This building block is an embryonic organ called the Neural Crest that later goes on to form important parts of the nervous system, but in addition it also forms major parts of the head and face, glands in the neck, the large arteries leading out from the heart, and pigment cells (melanocytes) in the skin. It is particularly important to gain insight into development of this organ because the tissues that derive from the neural crest are the most at risk for birth defects and for childhood cancers. Knowledge of neural crest development also tells us about our own evolution, because the neural crest is the only major system found only in vertebrates including humans.Read moreRead less
Understanding how the brain grows and is organised is one of the great challenges of science. This project seeks to identify key regulators of neural progenitors as these are the building blocks from which all brains cells are derived. This knowledge may also identify new avenues through which to manipulate neural progenitor function. This has implications not only for normal brain development but also potential therapies for neural disorders and disease.
Can Human Neural Stem Cells Form Enteric Nerves In Human Hirschsprungs Disease Colon?
Funder
National Health and Medical Research Council
Funding Amount
$598,815.00
Summary
The intestine has its own nervous system which develops from cells that migrate into the intestine during early development. Sometimes this does not work and part of the bowel has no nerves and cannot function. This is treated now by cutting out this bad bowel and joining the sections of good bowel. But it may be possible to grow new nerves in the bad bowel using stem cells. This project aims to test whether this treatment, which would avoid loss of bowel, is possible.
Neural Crest Stem Cell Therapy For Absence Of Intestinal Nerves In Hirschsprungs Disease
Funder
National Health and Medical Research Council
Funding Amount
$504,377.00
Summary
Hirschsprung's disease is acommon birth defect caused by failure of nerve cells to get into the colon. This results in intractable often fatal constipation. Current treatment is surgical removal of the affected colon soon after birth but often problems persist. These nerves might be rebuilt using nerve stem cells, but not all stem cells have this capacity. And is not known if this can be achieved after birth: This project will define which stem cell populations to use and in what age of bowel.
The Role Of GRHL-3, A Mammalian Homologue Of Drosophila Grainyhead, In Neural Tube Development
Funder
National Health and Medical Research Council
Funding Amount
$496,500.00
Summary
Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first ....Spina bifida and anencephaly are two common human congenital malformations that form part of a wide spectrum of mutations known collectively as neural tube defects (NTDs). Patients with the most severe form of spina bifida have a failure of the vertebral column and skin to close over the spinal cord and therefore suffer from limb paralysis and marked bladder and bowel dysfunction. Infants with anencephaly have an open cranial vault and failure of normal brain development and die within the first few hours of life. These abnormalities occur frequently (1-1000 live births) and are a direct result of failure of the neural tube to close during embryogenesis. NTDs are influenced by both environmental and genetic factors. The best characterised environmental factor is the dietary supplement folate, which when administered before conception results in a reduction in the incidence of spina bifida. The genetic complexity is evidenced by the array of mouse genetic mutations that give rise to NTDs. One of these mouse mutations, known as Curly tail (ct), has served as the major animal model of human NTDs. This is because the ct mice are resistant to folate administration (like most of the cases of spina bifida currently seen in patients) and because the mice seem to have normal development in virtually all other organ systems. Ironically, the genetic mutation that causes the curly tail phenotype has remained undiscovered for over 50 years. We have now identified the gene mutated in the curly tail mice. This gene is highly conserved in humans suggesting that it will play a similar role in neural tube development in man. The gene, known as GRHL-3, is a descendant of a fly gene critical for development of the nervous system in that organism. The studies we propose here will examine the developmental pathways involved in normal neural tube closure in mice and humans and will impact on our understanding of these devastating congenital malformations.Read moreRead less