The Developmental Genetics of Brain-Body Allometry

有机体变异最普遍的特征之一是形状与大小相关。这种异速变异是性状协变倾向的一个例子。整合与遗传变异相结合导致性状间的共变，使选择的表型反应成为可能，但也限制了表型反应。当发展过程驱动多种性状的变异时，整合就发生了。通过引导遗传和环境影响，整合赋予表型共变结构。理解这种结构是解决现代生物学中最困难的问题之一的关键——发育如何将复杂性状的遗传变异转化为表型变异——这是一个现代基因组方法尚未给出令人满意答案的问题。***我们的研究项目涉及形态变异的遗传、发育和环境决定因素。我们整合了多尺度成像，形态计量学和发育生物学。拟议的项目解决了异速发育的发展基础。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，形状与大小共变的发育基础实际上是未知的。这是一个更大的问题的关键入口，即发育如何结构表型变异的表达。我们专注于一个经典的例子-脑与身体质量（BM）的比例以及大小与颅面形状的关系。我们的项目有以下目的：***目的1：异速变异的遗传学：我们测试了重组近交系小鼠异速变异的遗传结构模型。***目的2：从个体发育到静态异速：在脑体异速变化的等基因重组近交系小鼠中，我们将个体发育的比例变化与给定年龄的异速关系联系起来。我们将3D成像与发育过程中的基因表达结合起来，以测试异速生长的机制模型。***目的3：基于摄动的异速生长分析。我们探索异速生长的机制在小鼠突变体与特定的扰动生长。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。体型的进化变化是常见的，异速变异虽然受到选择的影响，但对变化的方向产生偏见和限制。对体重的人工选择在生产动物中很常见，了解这种选择的异速后果及其潜在的发育机制对于预测或改变异速效应至关重要。最后，了解异速生长的发育基础将有助于形态学的发育遗传学。

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.