MESENCHYME AND OLFACTORY SYSTEM MORPHOGENESIS

间充质和嗅觉系统形态发生

基本信息

批准号：
2391074
负责人：
Raymond M ANCHAN
金额：
$ 1.65万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-04-01 至
项目状态：
未结题

项目摘要

This research proposal will determine whether, a distinct subpopulation of frontonasal mesenchyme identified by GAP-43 immunoreactivity in the mouse, is responsible for producing RA-inductive signals that regulate olfactory system morphogenesis. In PAX-6 mutant mice the olfactory system fails to develop, and this sub-population of GAP-43 immunoreactive mesenchymal cells is absent from the mutant PAX-6 mouse's frontonasal mesenchyme. Accordingly this study will test the hypothesis that, the GAP-43 immunoreactive mesenchymal cells are a distinct source of retinoid inductive signals that lead to the morphogenesis of the olfactory system. This hypothesis will be tested by addressing the following four specific aims. Specific Aim 1. To determine the position of the GAP-43 immunoreactive mesenchymal cells in the normal mouse. These experiments will show whether the GAP-43 immunoreactive mesenchymal population is located sufficiently close to retinoid responsive forebrain regions to provide the retinoid inductive signals. Specific Aim 2. To determine whether the GAP-43 immunoreactive mesenchymal cells produce retinoid signals. These studies will identify the source or sources of retinoid signals in the frontonasal mesenchyme and determine their relationship to the GAP-43 immunoreactive population of cells. Specific Aim 3. To assess the origin of the GAP-43 immunoreactive mesenchymal cells of the frontonasal mesenchyme. It is likely that the GAP-43 immunoreactive cells in the mouse frontonasal mesenchyme are derived from the neural crest since during development cranial crest cells migrate tot he frontonasal region (Matsuo et all., 1993). Therefore, populations of frontonasal mesenchyme that are neural crest derived will be identified by immunostaining the frontonasal mesenchyme with antibodies that recognize neural crest specific antigens. Specific Aim 4. To assess potentially ectopic sites of retinoic acid production along the migratory pathway of th neural crest to the frontonasal region in mutant PAX-6 mice. Since PAX-6 influences migration of neural crest to the frontonasal mesenchyme (Matsuo et al., 1993), these studies will determine whether the population of GAP-43 immunoreactive mesenchymal cells is ectopically positioned due to aberrant neural crest migration in PAX-6 mutant mice. In the embryonic mouse, the frontonasal mesenchyme is made up of a mosaic of cells, including a large population of post-migratory cranial neural crest cells (Le Douarin, 1983; 1986; 1993; Noden, 1975; 1988; Richman and Tickle, 1989; Serbedzija et al., 1992). Therefore, distinct subpopulations of ventrolateral mesenchyme may be derived from the neural crest. Specific Aim 1 will define the location of these mesenchymal populations relative to the developing olfactory system. Specific Aim 2 will determine whether the GAP-43 immunoreactive mesenchymal cells or any of the other antigenically distinct subpopulations of frontonasal mesenchyme provide RA signals during olfactory system development. Specific Aim 3 will then further characterize this retinoid-producing population of mesenchyme, by examining whether these cells share antigenic properties of neural crest cells indicative of their lineage. Since mutant PAX-6 animals show aberrant migration of neural crest as well as failed development of their olfactory systems, if the migrating neural crest cells are the source of RA-signals, then sites of ectopic RA production would be expected in the mutant PAX-6 mice. Accordingly mutant PAX-6 mice are an excellent system in which to test this hypothesis. Thus this work may define a distinct and transient sub lineage of neural crest cells distinguished by GAP-43 immunoreactivity that populates the frontonasal mesenchyme and is specialized to produce region specific inductive signals that regulate vertebrate forebrain morphogenesis.

这项研究建议将决定是否对通过gap-43在小鼠中通过GAP-43免疫反应鉴定的额骨间充质，负责产生调节嗅觉的RA诱导信号系统形态发生。在PAX-6突变小鼠中，嗅觉系统未能 GAP-43免疫反应性间充质细胞的这种亚群突变体PAX-6小鼠的额骨间充质不存在。因此，这项研究将检验以下假设：GAP-43 免疫反应性间充质细胞是类维生素的独特来源导致嗅觉系统形态发生的电感信号。该假设将通过解决以下四个特定的测试来检验目标。具体目的1。确定GAP-43免疫反应性的位置正常小鼠中的间充质细胞。这些实验将表明是否 GAP-43免疫反应性间充质群体足够接近类维生素性反应式前脑区域，以提供类维生素感应信号。具体目标2。确定GAP-43免疫反应性间充质是否是否细胞产生类维生素类似信号。这些研究将确定来源或额气中的类视黄素信号来源，并确定它们与GAP-43细胞的免疫反应性群体的关系。特定目的3。评估GAP-43免疫反应性的起源额骨间充质的间充质细胞。很可能小鼠额骨间充质中的GAP-43免疫反应性细胞得出从自发颅纹细胞迁移以来的神经rest 额叶区域（Matsuo et all。，1993）。因此，人口将识别出神经rest的额骨间充质的通过免疫抑制额间质，并用抗体识别神经rest特异性抗原。特定目的4。评估视黄酸的潜在异位部位沿着神经rest的迁移途径的生产突变体PAX-6小鼠中的额骨区域。由于PAX-6影响迁移神经rest到额骨的间充质（Matsuo等，1993），这些研究将确定GAP-43免疫反应性的种群是否间充质细胞因异常神经rest而异位位置 PAX-6突变小鼠中的迁移。在胚胎小鼠中，额骨间充质由马赛克组成细胞，包括大量的媒介后颅神经波峰细胞（Le Douarin，1983; 1986; 1986; 1993; Noden，1975; 1988; Richman and richman and d Tickle，1989年； Serbedzija等，1992）。因此，不同的亚群腹外侧间充质的含量可以源自神经rest。具体的 AIM 1将定义这些间充质种群的位置发展中的嗅觉系统。具体目标2将确定是否 GAP-43免疫反应性间充质细胞或其他任何抗原额骨间充质的不同亚群提供了RA信号嗅觉系统开发。特定的目标3将进一步通过研究这些细胞是否具有神经rest细胞的抗原特性指示其血统。由于突变PAX-6动物表现出异常神经rest的迁移以及嗅觉的发展失败系统，如果迁移的神经rest细胞是Ra-Signals的来源，则然后，突变体PAX-6的异位RA产生的位点将被预期老鼠。因此，突变体PAX-6小鼠是一个极好的系统检验此假设。因此，这项工作可以定义一个独特的瞬态通过GAP-43免疫反应性区分的神经rest细胞的子谱系填充了额骨的间充质，并且专门生产调节脊椎动物前脑的区域特异性电感信号形态发生。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Immunocytochemical evidence for co-expression of Type III IP3 receptor with signaling components of bitter taste transduction.

DOI：
10.1186/1471-2202-2-6
发表时间：
2001
期刊：
BMC neuroscience
影响因子：
2.4
作者：
Clapp TR;Stone LM;Margolskee RF;Kinnamon SC
通讯作者：
Kinnamon SC

Functional nonequality of the cardiac and skeletal ryanodine receptors.

心脏和骨骼兰尼碱受体的功能不均匀。

DOI：
10.1073/pnas.94.3.1019
发表时间：
1997
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Nakai,J;Ogura,T;Protasi,F;Franzini-Armstrong,C;Allen,PD;Beam,KG
通讯作者：
Beam,KG