The earliest developmental origins of dysmorphologies are poorly understood in many congenital diseases. They often remain elusive because the first signs of genetic misregulation may initiate as subtle changes in gene expression, which are hard to detect and can be obscured later in development by secondary effects. Here, we develop a method to trace back the origins of phenotypic abnormalities by accurately quantifying the 3D spatial distribution of gene expression domains in developing organs. By applying Geometric Morphometrics to 3D gene expression data obtained by Optical Projection Tomography, we determined that our approach is sensitive enough to find regulatory abnormalities that have never been detected previously. We identified subtle but significant differences in the gene expression of a downstream target of a Fgfr2 mutation associated with Apert syndrome, demonstrating that these mouse models can further our understanding of limb defects in the human condition. Our method can be applied to different organ systems and models to investigate the etiology of malformations.

No abstract

In the last years, there has been a big effort to identify risk factors for reading difficulties and to develop new methodologies to help struggling readers. It has been shown that early intervention is more successful than late intervention, and that intensive training programs can benefit children with reading difficulties. The aim of our study is to investigate the effectiveness of an intensive computerized phonological training program designed to improve reading performance in a sample of children with reading difficulties at the early stages of their reading learning process. Thirty-two children with reading difficulties were randomly assigned to one of the two intervention groups: RDIR (children with reading difficulties following a computerized intensive remediation strategy) (n = 20) (7.01 ± 0.69 years), focused on training phonemic awareness, decoding and reading fluency through the computational training; and RDOR (children with reading difficulties following an ordinary remediation strategy) (n = 12) (6.92 ± 0.82 years), which consisted of a reinforcement of reading with a traditional training approach at school. Normal readers (NR) were assigned to the control group (n = 24) (7.32 ± 0.66 years). Our results indicate that both the RDIR and RDOR groups showed an increased reading performance after the intervention. However, children in the RDIR group showed a stronger benefit than the children in the RDOR group, whose improvement was weaker. The control group did not show significant changes in reading performance during the same period. In conclusion, results suggest that intensive early intervention based on phonics training is an effective strategy to remediate reading difficulties, and that it can be used at school as the first approach to tackle such difficulties.

16The earliest developmental origins of dysmorphologies are poorly understood in many congenital 17 diseases. They often remain elusive because the first signs of genetic misregulation may initiate as 18 subtle changes in gene expression, which can be obscured later in development due to secondary 19 phenotypic effects. We here develop a method to trace back the origins of phenotypic abnormalities by 20 accurately quantifying the 3D spatial distribution of gene expression domains in developing organs. By 21 applying geometric morphometrics to 3D gene expression data obtained by Optical Projection 22 Tomography, our approach is sensitive enough to find regulatory abnormalities never previously 23 detected. We identified subtle but significant differences in gene expression of a downstream target of 24 the Fgfr2 mutation associated with Apert syndrome. Challenging previous reports, we demonstrate that 25Apert syndrome mouse models can further our understanding of limb defects in the human condition. 26Our method can be applied to other organ systems and models to investigate the etiology of 27 malformations. 28

No abstract