Seminar

A journey through development and its associated diseases

Rosa Barrio, PhD

Animal development is regulated by intrinsic (genetic) and extrinsic (environmental) cues. In humans, deviations in this process often originate from physical or physiological alterations that underlie the etiology of many rare diseases. The factors involved in the regulation of development are conserved throughout evolution. Among them, SUMO (small ubiquitin-like modifier), which is conjugated/deconjugated to target proteins, thus changing their properties. We discovered that SUMO is involved in the regulation of the synthesis of steroid hormones, controlling the size of the organism and its transition to adulthood. In order to study these processes in vivo, we developed specific technology easy to use and accessible to most laboratories, to identify SUMOylated proteins as well as proteins modified by other ubiquitin-like factors. SUMO frequently modifies transcription factors, influencing their capacity to regulate target genes. Among them, the members of the Spalt-like family of zinc finger transcription factors (SALL) are SUMOylated, changing both their function and localization. Mutations in SALL genes cause hereditary human diseases, such as the Townes-Brocks and the Okihiro syndromes, in which patients exhibit polydactyly, hearing impairment and kidney problems, among other symptoms. We discovered that cells derived from a Townes-Brocks patient have defective primary cilia, cellular organelles essential for cell signaling, and this likely contributes to the etiology of the disease. By using state-of-the art biotechnology, genomics and proteomics we explore the mechanistic insights of this syndrome. An overview of the past, current and future work of the laboratory in relation to these processes will be presented.