CDK13-related disorder, also known as congenital heart defects, dysmorphic facial features and intellectual developmental disorder (CHDFIDD) is associated with mutations in the CDK13 gene encoding transcription-regulating cyclin-dependent kinase 13 (CDK13). Here, we focused on the development of craniofacial structures and analyzed early embryonic stages in CHDFIDD mouse models, with one model comprising a hypomorphic mutation in Cdk13 and exhibiting cleft lip/palate, and another model comprising knockout of Cdk13, featuring a stronger phenotype including midfacial cleft. Cdk13 was found to be physiologically expressed at high levels in the mouse embryonic craniofacial structures, namely in the forebrain, nasal epithelium and maxillary mesenchyme. We also uncovered that Cdk13 deficiency leads to development of hypoplastic branches of the trigeminal nerve including the maxillary branch. Additionally, we detected significant changes in the expression levels of genes involved in neurogenesis (Ache, Dcx, Mef2c, Neurog1, Ntn1, Pou4f1) within the developing palatal shelves. These results, together with changes in the expression pattern of other key face-specific genes (Fgf8, Foxd1, Msx1, Meis2 and Shh) at early stages in Cdk13 mutant embryos, demonstrate a key role of CDK13 in the regulation of craniofacial morphogenesis.

• Keywords
• Axons, CDK13, Craniofacial development, Neurite outgrowth, Orofacial clefts, Trigeminal ganglion,
• MeSH
• Cyclin-Dependent Kinases metabolism   genetics   MeSH
• Embryo, Mammalian metabolism   MeSH
• Embryonic Development * genetics   MeSH
• Phenotype MeSH
• Skull embryology   pathology   MeSH
• Intellectual Disability genetics   MeSH
• Disease Models, Animal * MeSH
• Mutation genetics   MeSH
• Mice MeSH
• Trigeminal Nerve embryology   MeSH
• Neurogenesis * genetics   MeSH
• Face embryology   abnormalities   MeSH
• Doublecortin Protein MeSH
• Cleft Palate genetics   pathology   embryology   MeSH
• Cleft Lip genetics   pathology   embryology   MeSH
• Gene Expression Regulation, Developmental * MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cyclin-Dependent Kinases MeSH
• Dcx protein, mouse MeSH Browser
• Doublecortin Protein MeSH

The advent of high-resolution imaging has made data on surface shape widespread. Methods for the analysis of shape based on landmarks are well established but high-resolution data require a functional approach. The starting point is a systematic and consistent description of each surface shape and a method for creating this is described. Three innovative forms of analysis are then introduced. The first uses surface integration to address issues of registration, principal component analysis and the measurement of asymmetry, all in functional form. Computational issues are handled through discrete approximations to integrals, based in this case on appropriate surface area weighted sums. The second innovation is to focus on sub-spaces where interesting behaviour such as group differences are exhibited, rather than on individual principal components. The third innovation concerns the comparison of individual shapes with a relevant control set, where the concept of a normal range is extended to the highly multivariate setting of surface shape. This has particularly strong applications to medical contexts where the assessment of individual patients is very important. All of these ideas are developed and illustrated in the important context of human facial shape, with a strong emphasis on the effective visual communication of effects of interest.

• Keywords
• asymmetry, functional data, human faces, shape, surface data, visualisation,
• Publication type
• Journal Article MeSH