The evolution and development of cell number and organ size

细胞是所有多细胞生物的基石，细胞数量的变化对生物体的形态、功能和进化有着重要的影响。细胞数量的进化变化可以改变单个器官和身体结构的外观和生理，因此有助于生物多样性。不正确的细胞数量规格导致器官发育过大或过小，细胞数量不受控制的扩张导致癌症。因此，了解细胞数量的调节对于扩大我们对器官大小和功能的规范、动植物形状和大小的进化以及包括癌症在内的疾病的遗传和发育基础的认识至关重要。因此，充分描述调节细胞数量的发育机制和遗传因素是至关重要的，特别是在对器官大小的规范知之甚少的情况下。筛选新基因和研究影响细胞数量的已知基因和途径的功能，为细胞数量的调控提供了许多见解。然而，研究细胞数量的自然变化提供了一种有力的方法来补充这些其他策略。这是因为在细胞数量和器官大小上表现出自然变化的生物体必须包含和表达导致这些变化的遗传和发育变化。因此，确定生物之间细胞数量自然变化的遗传和发育基础不仅可以揭示这些变化是如何进化的，而且可以为这些过程如何被调节提供新的见解。在这个提案中，我们将描述导致细胞数量自然差异的发育变化，这种差异导致果蝇的眼睛每只眼睛中有多达5000个细胞的大小差异。我们还将绘制细胞数量变化背后的遗传变异，并研究这些变化如何改变眼睛大小的遗传调控。除了揭示细胞数量进化差异的发育和遗传基础外，这将为细胞数量的规范提供新的见解，这些数据将用于生成预测模型，以更广泛地了解动物细胞数量和器官大小的调节。

Cells are the building blocks of all multicellular organisms and changes in cell number have important consequences for organismal form, function and evolution. Evolutionary changes in cell number can alter the appearance and physiology of individual organs and body plans, and therefore contribute to organismal diversity. Incorrect specification of cell number results in the development of organs that are too large or too small, and uncontrolled expansion of cell number results in cancer.Therefore, understanding the regulation of cell number is vital to expanding our knowledge about the specification of organ size and function, the evolution of the shape and size of plants and animals, and the genetic and developmental bases of diseases including cancer. It follows that it is essential to fully describe the developmental mechanisms and genetic factors that regulate cell number especially in the case of the specification of organ size about which little is known.Screening for new genes and studying the function of known genes and pathways that affect cell number has provided many insights into the regulation of cell number. However, studying natural variation in cell number provides a powerful approach that compliments these other strategies. This is because organisms that exhibit natural variation in cell number and organ size must contain and express the genetic and developmental changes that cause these changes. Therefore, identifying the genetic and developmental bases of natural variation in cell number between organisms will not only reveal how these changes have evolved but provides new insights into how these processes are regulated.In this proposal we will describe the changes in development that cause natural differences in cell number that cause the eyes of Drosophila to be larger or smaller by up to 5000 cells in each eye. We will also map the genetic variants underling these changes in cell number and investigate how these changes alter the genetic regulation of eye size. As well as revealing the developmental and genetic bases of evolutionary differences in cell number, this will provide new insights into the specification of cell number, and this data will be used to generate predictive models to understand the regulation of cell number and organ size in animals more broadly.