The Developmental Genetics of Brain-Body Allometry

生物体变异最普遍的特征之一是形状与大小1相关。这种异速生长变异是整合或性状协同变化的一个例子。整合与遗传变异相结合，导致性状之间的协变，这使得对选择的表型反应成为可能，但也限制了表型反应。当发育过程驱动多个特征的变异时，整合就发生了。通过引导遗传和环境影响，整合赋予表型协变结构。了解这种结构是现代生物学中最困难的问题之一，也是发育如何将遗传转化为复杂性状的表型变异的关键，这是现代基因组学方法尚未给出满意答案的问题。*我们的研究项目致力于形态变异的遗传、发育和环境决定因素。我们集成了多尺度成像、形态计量学和发育生物学。拟议的项目解决了异速生长的发展基础。异速生长在比较模式和数量遗传学方面得到了很好的研究。然而，形状与大小共同变化的发育基础几乎是未知的。这是一个更大的问题的关键条目，即发育如何构建表型变异的表达。我们集中在一个经典的例子，大脑与身体质量的比例(BM)以及大小与头面部形状的关系。我们的项目有以下目标：*目标1：异速生长遗传学：我们测试了重组近交系小鼠异速生长变异的遗传结构模型。*目标2：从个体发育到静态异速生长：在脑-体异速生长不同的等基因重组近交系小鼠中，我们通过个体发育将比例变化与给定年龄的异速生长关系联系起来。我们将3D成像与发育过程中的基因表达相结合，以测试异速生长的机制模型。*目标3：基于扰动的异速生长分析。我们探索了具有特定生长扰动的小鼠突变体的异速生长机制。*每个目标都是独立的，但共同揭示了大脑大小和面部形状异速生长变异的发育遗传学。这项工作对进化生物学、生产动物生物学和复杂性状遗传学具有重要意义。大小的进化变化是常见的，异速生长变化虽然受到选择的影响，但对变化的方向产生了偏见和制约。人工选择体重在生产动物中很常见，了解这种选择的异速生长结果及其背后的发育机制对于预测或改变异速生长效应至关重要。最后，了解异速生长的发育基础将对形态的发育遗传学有很大的帮助。

One of the most ubiquitous features of organismal variation is that shape correlates with size 1. This allometric variation is an example of integration or the tendency for traits to covary. Integration combined with genetic variation results in covariation among traits that enables but also restricts phenotypic responses to selection. Integration occurs when developmental processes drive variation in multiple traits. By channeling genetic and environmental influences, integration imparts structure on phenotypic covariation. Understanding this structure is key to one of the most difficult problems in modern biology how development translates genetic to phenotypic variation in complex traits a question to which modern genomic approaches have not yielded satisfactory answers. *** Our research program addresses the genetic, developmental and environmental determinants of morphological variation. We integrate multi-scale imaging, morphometrics and developmental biology. The proposed project tackles the developmental basis for allometry. Allometry is well studied in terms of comparative patterns and quantitative genetics. Yet, the developmental basis for the covariation of shape with size is virtually unknown. This is a key entry to the larger question of how development structures the expression of phenotypic variation. We focus on a classic example the scaling of brain to body mass (BM) and the relation of size to craniofacial form. Our project has the following aims:*** Objective 1: Genetics of Allometry: We test a model for the genetic architecture of allometric variation in recombinant inbred mice.*** Objective 2: From Ontogenetic to Static Allometry: In isogenic recombinant inbred mouse strains that vary in brain-body allometry, we connect proportional changes through ontogeny with allometric relationships at a given age. We integrate 3D imaging with gene expression during development to test mechanistic models of allometry.*** Objective 3: Perturbation-based analysis of allometry. We probe mechanisms of allometry in mouse mutants with specific perturbations to growth.*** Each aim is independent, but together reveal the developmental genetics of allometric variation in brain size and facial shape. This work is important for evolutionary biology, production animal biology and complex traits genetics. Evolutionary changes in size are common and allometric variation, while influenced by selection, produces bias and constraint on the directions of change. Artificial selection for body mass is common in production animals and understanding the allometric consequences of that selection and the developmental mechanisms that underlie is critical for predicting or altering allometric effects. Finally, understanding the developmental basis for allometry will contribute significantly towards the developmental-genetics of morphology.