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。理解这种结构是现代生物学中最困难的问题之一的关键，即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得出令人满意答案的问题。

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.