Developmental canalization in the human head

Targeted and precise organismal development, buffered against environmental and genetic perturbations, is a prerequisite for the development and evolution of complex life. Evidence increases that a disruption of this developmental "canalization" underlies a broad range of human diseases with unclear etiology. Contemporary biology has uncovered many of the central processes in animal development, but we still know surprisingly little about the mechanisms that stabilize these processes and guide perturbed development back to its target trajectory. The cranium is the most complex skeletal structure in the human body, housing the brain and the sensory organs, the airways as well as the masticatory apparatus. Precise and well-coordinated growth of cranial components thus is an inevitable prerequisite of functional development of the human head. In the proposed project, we will investigate temporal and spatial patterns of developmental canalization in the human head along with its genetic basis and clinical relevance by combining a wide range of theoretical and empirical analyses. We will develop a comprehensive mathematical and statistical theory of developmental canalization that enables the discovery and quantification of the central properties of canalization in observed growing individuals. We integrate this novel methodology into contemporary morphometrics and image analysis in order to apply it to longitudinal series of X-ray images, covering the full period of postnatal human cranial growth. We will use longitudinal X-ray images of twins as well as three-dimensional CT scans and surface scans of genotyped individuals to investigate the quantitative genetic basis of canalization. In patients after craniofacial surgery (mandibular sagittal split osteotomy), we will model relapse during post-operative bone remodeling as canalization towards an undesired target trajectory. This may contribute to optimal treatment planning with minimal relapse.

Targeted and precise organismal development, buffered against environmental and genetic perturbations, is a prerequisite for the development and evolution of complex life. A disruption of this developmental "canalization" underlies a broad range of human diseases with unclear etiology, but we still know surprisingly little about the mechanisms that guide perturbed development back to its target trajectory. The goal of this FWF project was to investigate developmental canalization in the human head. To this end we developed a model of developmental canalization and showed how to estimate the strength of canalization and the actually canalized variance in a population even if the target trajectories are unobserved. In an application to a longitudinal X-ray study, we found that craniofacial size is strongly canalization during the first 5 years of life. Frontal sinus size, by contrast, did not show any signs of canalization. Different features of craniofacial shape showed very different developmental dynamics. Whereas the relative dimensions of the nasopharynx showed strong canalization and a reduction of variance throughout postnatal development, facial orientation continually increased in variance. These results on the pattern and timing of developmental canalization in the human cranium can be used to identify the underlying molecular and developmental mechanisms and to optimize the effective timing of orthodontic and surgical treatment. We are currently applying these methods to study relaps (as a form of pathological canalization) after craniofacial surgery. Using both morphometric and genetic data, we are also assessing the genetic architecture of variation and canalization of craniofacial shape. We also developed new morphometric methods to study the generation and canalization of morphological variance. In particular, we demonstrated how to separate morphometric variation at different spatial scales. We showed that compensatory growth processes at small spatial scale can underly the canalization of variance at larger scales. For instance, we found that many functional aspects of cranial shape are highly canalized even though the relative dimensions of the constituting bones vary considerably across individuals. We proposed that epigenetic mechanisms of compensatory growth are a key factor in the targeted growth of complex structures, such as the vertebrate cranium. We extended current morphometric methodology to compare canalization of symmetric and asymmetric variation of cranial shape in different groups. In an application to human and great ape endocranial shape (the part of the cranium encapsulating the brain), we found that the average spatial asymmetry pattern, previously considered to be uniquely human, was shared among humans and apes. In humans, however, it was less directed, and different local asymmetries were less correlated. We, thus, found human asymmetry to be much more variable - less canalized - compared with that of apes. These findings likely reflect increased functional and developmental modularization of the human brain.