Developmental disorders Journal Meeting: a collaboration between Development and Disease Models & Mechanisms.

Abstract

Developmental disorders present at birth or arise during childhood, leading to physical or intellectual disabilities with long-term effects on morbidity. According to a study from the Centers for Disease Control and Prevention, one in six children in the USA has a developmental disability that affects their education and lifestyle (Zablotsky et al., 2019). These disorders encompass a wide range of conditions, and are caused by genetic and/or environmental factors. Expanding research in this area is fundamental to improving diagnosis, preventing progression and treating these conditions. At DiseaseModels &Mechanisms (DMM), we have a strong interest in research that delineates the mechanisms that underlie developmental disorders, with a dedicated collection of Reviews, Perspectives and Research articles. We pursue pre-clinical modelling to discover new mechanistic insights with a view towards how this can support children and their families, and inform their care. This year, DMM has joined with sister journal Development to bring together developmental biologists, disease modellers, human geneticists and clinicians to address the most-pressing issues within this field. The Company of Biologists Journal Meeting ‘Developmental Disorders: From Mechanism to Treatment’ will be held on 14–17 September 2021 (Box 1). This virtual Meeting, organised by Phil Beales (University College London, UK), Development Editor-in-Chief James Briscoe (The Francis Crick Institute, London, UK), DMM Editor Monica J. Justice (The Hospital for Sick Children, Toronto, Canada) and Lee Niswander (University of Colorado, Boulder, CO), will build and strengthen connections between disciplines, and encourage researchers and clinicians to share their perspectives to drive progress. Patients will also share their journeys living with these disorders. We believe that the patient’s perspective is crucial for a holistic understanding of the disease and can help to unify the unmet needs of this research. Genetics play a pivotal role in the causation of many developmental disorders including rare diseases. This years’ Meeting will address how advances in genetic technology can be applied to the discovery of causative genetic variants for rare developmental diseases. Animal models of rare developmental disorders are key to understanding the mechanisms and whole-body physiological effects of mutations, especially given the challenges of the small patient cohorts. Research published by DMM exploring this and other genetic mechanisms that underlie rare disease can be found in the collection ‘Rare Disease Translational Research Using Model Systems’. In one study, understanding the genetic cause of the rare neurodevelopmental disorder Rett syndrome identified a novel treatment in which a small neurotrophin receptor-targeting molecule can reduce respiratory and motor control deficiencies in a pre-clinical mouse model (Adams et al., 2020). Unlike monogenic disorders, in which mutations within a single gene cause the particular disease, certain developmental disorders can be caused by variants of multiple genes that can converge to affect a singular organelle (Abdelhamed et al., 2020; Falkenberg et al., 2021; Lange et al., 2021). Ciliopathies, which will be discussed at the Meeting, are caused by defects in motile and nonmotile cilia that act as signalling organelles extending from the surface of most eukaryotic cells. As cilia are found in most cells, mutations in cilia components can lead to developmental defects in multiple organs and tissues, including the brain, bones, kidneys and sensory organs. Genes associated with ciliopathies often have high variability in their phenotypic effects; therefore, it is particularly important to study the effects of missense variations – rather than gene depletion – on a disease phenotype to accurately mirror the genetic presentation in patients. Joubert syndrome is a ciliopathy that primarily affects brain development and devastatingly reduces life expectancy to under 10 years of age. This disease is associated 1The Company of Biologists, Station Road, Histon, Cambridge CB24 9LF, UK. 2Program in Genetics and Genome Biology, The Hospital for Sick Children, and Department of Molecular Genetics, The University of Toronto, Toronto, Ontario M5G 0A4, Canada. 3MRC Human Genetics Unit and Cancer Research UK Edinburgh Centre, MRC Institute of Genetics and Cancer, The University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK.