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The Evolution of Posterior Fate

后命运的演变

基本信息

批准号：
1926802
负责人：
Nir Yakoby
金额：
$ 85.74万
依托单位：
Rutgers University Camden
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1926802&HistoricalAwards=false
关键词：
Evolution Posterior Fate

项目摘要

The evolution of body shape and body axes relies on changes to regulatory networks that control tissues' development across organisms. The grant will examine how changes in the regulatory network of genes in one species can be changed and lead to the formation of morphological novelties in other species. Uncovering the natural changes underlying morphological diversity among species will shed light on organ formation strategies. The preliminary results demonstrate the successful use of a genome engineering technique in non-traditional species, which will allow the principal investigator to establish them as new model systems to study how changes in gene regulation control the evolution of new morphologies. The studied signaling pathways and transcription factors are conserved in other animals, hence the Drosophila community and other developmental communities will gain knowledge on these pathways and benefit from the generated genetic tools. A Postdoctoral trainee, a Ph.D. student, and 9 undergraduate students will be trained in fly genetics, molecular biology, bioinformatics and genome engineering, with an emphasis on trainees from underrepresented minorities in the STEM fields. The data generated will be incorporated into the Genetics class curricula at the level of graduate and undergraduate studies, which serves about 60 students annually. The principal investigator will reach out to prospective biology students and their families from the Camden, NJ area during the biology visiting days.Axis formation is a fundamental requirement during animal development. This intricate process is regulated by a small number of highly-conserved cell signaling pathways across animals. The principal investigator (PI) will study the evolution of gene regulatory networks, comprised of the epidermal growth factor receptor (EGFR), the Janus Kinase (JAK/STAT), bone morphogenetic protein (BMP), and transcriptional regulators that control the anterior posterior axis in Drosophila melanogaster. The PI suggests that components of the network evolved from controlling axis formation during fly oogenesis to also regulating the formation of a morphological novelty, the dorsal ridge, on the D. nebulosa eggshells. The PI's laboratory pioneered the molecular analysis of dorsal ridge formation by discovering the dramatic changes in EGFR activation patterns among species. The PI hypothesizes that changes in cis regulation of genes controlling the posterior fate in one species evolved to guide the generation of a new morphology in other species. The preliminary results demonstrate that the ETS-transcription factor Pointed (PNT) controls the expression of the posterior determinant Midline (Mid). Research goals are to, a) determine the network controlling patterning of the posterior end, b) study the cis regulatory modules controlling mid expression and 3), study whether changes in MID patterning control the evolution of the dorsal ridge. Using a combination of immunostaining, genetic perturbations, including CRISPR/Cas9, and reciprocal swapping of orthologous CRMs, the function, requirement, and redundancy of these CRMs will be tested for patterning and morphogenesis in both D. melanogaster and D. nebulosa.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

身体形状和身体轴的进化依赖于控制生物体组织发育的调节网络的变化。该基金将研究一个物种的基因调控网络的变化如何改变，并导致其他物种的形态学新颖性的形成。揭示物种间形态多样性背后的自然变化将有助于阐明器官形成策略。初步结果表明基因组工程技术在非传统物种中的成功使用，这将使首席研究员能够将它们建立为新的模型系统，以研究基因调控的变化如何控制新形态的进化。所研究的信号通路和转录因子在其他动物中是保守的，因此果蝇群体和其他发育群体将获得关于这些通路的知识，并从所产生的遗传工具中受益。一个博士后，一个博士。将对2010年的2011名本科生和9名本科生进行果蝇遗传学、分子生物学、生物信息学和基因组工程方面的培训，重点是来自STEM领域代表性不足的少数民族的受训人员。产生的数据将被纳入遗传学类课程的研究生和本科生的研究水平，每年约60名学生。首席研究员将接触未来的生物学学生和他们的家庭从卡姆登，新泽西州地区在生物访问日。轴形成是动物发育过程中的基本要求。这个复杂的过程是由动物中少数高度保守的细胞信号通路调节的。主要研究者（PI）将研究基因调控网络的演变，包括表皮生长因子受体（EGFR），Janus激酶（JAK/STAT），骨形态发生蛋白（BMP）和控制果蝇前后轴的转录调控因子。PI表明，网络的组成部分从控制轴的形成在苍蝇卵子发生也调节形成的形态新奇，背脊，在D。雾状蛋壳。PI的实验室通过发现物种间EGFR激活模式的巨大变化，开创了背嵴形成的分子分析。PI假设在一个物种中控制后命运的基因的顺式调节的变化进化为指导其他物种中新形态的产生。初步结果表明，ETS-转录因子Pointed（PNT）控制后决定因子Midline（Mid）的表达。研究目标是，a）确定控制后端图案化的网络，B）研究控制MID表达的顺式调节模块，以及3）研究MID图案化的变化是否控制背脊的进化。使用免疫染色，遗传扰动（包括CRISPR/Cas9）和orthogonal CRMs的相互交换的组合，这些CRMs的功能，需求和冗余将在D.黑腹果蝇D.该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。