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Proximo-Distal Patterning in the Drosophila Appendages

果蝇附肢的近远端模式

基本信息

批准号：
9084854
负责人：
RICHARD S MANN
金额：
$ 7.01万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-01-01 至 2018-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9084854
关键词：
Address Animals Ankle Attention Binding Biological Models Cells Chest Congenital Abnormality Data Development Developmental Biology Diabetes Mellitus Distal Dorsal Drosophila genus Drosophila melanogaster Embryo Embryonic Development Enhancers Epidermal Growth Factor Receptor Eye Development Fingers Funding Gene Targeting Genes Genetic Genetic Transcription Goals Homologous Gene Knowledge Lead Leg Ligands Logic Malignant Neoplasms Medial Methods Modeling Molecular Genetics Names Nuclear Organogenesis Ovum Pathway interactions Pattern Positioning Attribute Primordium Process Proteins Receptor Signaling Research Project Grants Role Signal Pathway Sister Staging Testing Tissues Wing Work appendage cofactor fly genetic analysis homeodomain human disease insight man morphogens public health relevance research study stem cell biology tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): This project addresses fundamental questions in developmental biology using the developing leg of Drosophila melanogaster as the model system. In addition to having antero-posterior (AP) and dorso- ventral (DV) axes, the mature leg, as all appendages, also has a proximo-distal (PD) axis. Unlike the AP and DV axes, the PD axis must form de novo, within each thoracic hemisegment of a developing embryo. In the fly, the leg primordia are first identifiable as a cluster of ~30 cells that express the homeodomain-encoding Distalless (Dll) gene. By the end of larval development, the presumptive leg has ~20,000 cells and several defined domains along the PD axis. The goal of this project is understand how these cells obtain their positional information. Generally, a 'bottom-up' approach is used, in which cis-regulatory modules (CRMs) that drive the expression of PD genes are dissected in detail, to identify the upstream inputs that control their activities. In ths way, a network of CRM and gene activities will be generated. In the next funding period, particular attention will be given to 1) the most proximal PD domain, which co-expresses homothorax (hth), which encodes a homeodomain transcription factor, and teashirt (tsh), which encodes a Zn-finger nuclear factor and 2) the most distal PD domain, which is further elaborated due to the activities of the Epidermal Growth Factor Receptor pathway. In addition, the role of two 'ventral-identity' factors, encoded by the Drosophila homologs of vertebrate Sp8, dSp1 and buttonhead (btd), will be investigated, using both a CRM-centric and target gene approaches. Altogether, these experiments will lead to a better understanding of how positional information is generated in dividing cells, using transcription factors and signaling pathways that are conserved from flies to man.

描述（由申请人提供）：该项目使用果蝇的发育腿作为模型系统来解决发育生物学中的基本问题。除了具有前后（AP）和背腹（DV）轴之外，成熟的腿和所有的附属物一样，也具有近远（PD）轴。与AP和DV轴不同，PD轴必须在发育胚胎的每个胸半节内从头形成。在果蝇中，腿原基首先被鉴定为表达同源结构域编码Distalless（Dll）基因的约30个细胞的簇。到幼虫发育结束时，假定的腿具有约20，000个细胞和沿PD轴沿着的几个定义域。这个项目的目标是了解这些细胞如何获得它们的位置信息。通常，使用“自下而上”的方法，其中详细解剖驱动PD基因表达的顺式调节模块（CRM），以鉴定控制其活性的上游输入。通过这种方式，将产生CRM和基因活动的网络。在下一个资助期内，将特别关注1）最近端PD结构域，其共表达homothorax（hth）（编码同源结构域转录因子）和teashirt（tsh）（编码锌指核因子），以及2）最远端PD结构域，其由于表皮生长因子受体途径的活性而进一步阐述。此外，两个“腹认同”的因素，编码的果蝇同源脊椎动物Sp8，dSp1和buttonhead（btd）的作用，将进行调查，使用CRM为中心的和靶基因的方法。总之，这些实验将导致更好地理解位置信息是如何在分裂细胞中产生的，使用转录因子和信号通路，从苍蝇到人类都是保守的