Unequal Cleavage and D Quadrant Specification in the Leech Helobdella

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。胚胎发育需要精心安排的细胞分裂和其他过程，从单个细胞，受精卵，到成年形式。在每个发育阶段产生的细胞注定要通过相互作用的内在因素（遗传自它们的祖先）和外在线索（如邻近细胞产生的信号分子）对下一阶段做出特定的贡献。我们知道，影响这些“命运决定”的细胞和分子机制的基本“工具包”在物种之间是高度保守的。因此，了解工具包是如何在不同物种中部署的，包括相对简单、更容易研究的物种，如水蛭，可以有助于理解不同种类的动物如何进化出不同的成年身体计划，细胞命运过程如何在人类发育中起作用，以及故障如何导致癌症和出生缺陷等疾病。本研究旨在研究2细胞水蛭胚胎中发生的一种特殊细胞分裂，验证内在因素（局部钙离子浓度升高）和外在信号（邻近细胞分泌的一种名为WNT的高度保守蛋白）之间的相互作用导致受体细胞分裂不均的假设，产生一个子细胞注定为发育中的胚胎贡献肌肉、神经和皮肤，而另一个则注定主要为肠道贡献。Weisblat博士的研究还为博士后研究人员、本科生和研究生提供严格和具有成本效益的细胞和发育生物学技术培训，以及分析思维和写作的关键技能培训，其中许多人已经在医学、生物技术、科学政策、教学和研究方面进行了研究。除了招募和指导一个多元化的研究小组外，Weisblat博士还是NSF REU Site项目的主任，该项目旨在改善从代表性不足的少数民族中招收生物科学学生攻读博士学位的情况。他还通过在巴西、爱沙尼亚、印度、墨西哥和尼日利亚等发展中国家教学，努力促进科学的亲善。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Embryonic development entails exquisitely orchestrated cell divisions and other processes leading from a single cell, the fertilized egg, to the adult form. Cells arising at each stage of development become fated to make a particular contribution to the next stage via interacting intrinsic factors (inherited from their progenitors) and extrinsic cues (such as signaling molecules produced by neighboring cells). We know that a basic "toolkit" of cellular and molecular mechanisms influencing these "fate decisions" is highly conserved from species to species. Thus, understanding how the toolkit is deployed in various species, including comparatively simple, more easily studied ones such as the leech, can contribute to understanding how diverse kinds of animals evolved their distinct adult body plans, how cell fating processes function in human development and how malfunctions can result in disorders such as cancer and birth defects.This proposal is to study a particular cell division occurring in the 2-cell leech embryo, testing the hypothesis that interactions between intrinsic factors (locally elevated calcium ion concentrations) and extrinsic signals (a highly conserved protein called WNT secreted from the adjacent cell) cause the recipient cell to divide unequally, yielding one daughter cell fated to contribute muscle, nerves and skin to the developing embryo, and another fated to contribute mainly to the gut. Dr. Weisblat's research also provides rigorous and cost-effective training in cell and developmental biology techniques and in the critical skills of analytical thinking and writing for postdoctoral researchers, undergraduate and graduate students, many of whom have gone on to studies in medicine, biotechnology, science policy, teaching and research. In addition to recruiting and mentoring a diverse research group, Dr. Weisblat is director for an NSF REU Site program aimed at improving the recruitment of bioscience students from underrepresented minorities to Ph.D. studies. He has also worked to promote scientific goodwill by teaching in developing nations such as Brazil, Estonia, India, Mexico and Nigeria.