GemC1 governs multiciliogenesis through direct interaction with and transcriptional regulation of p73
JOURNAL OF CELL SCIENCE
Authors: Lalioti, Maria-Eleni; Arbi, Marina; Loukas, Ioannis; Kaplani, Konstantina; Kalogeropoulou, Argyro; Lokka, Georgia; Kyrousi, Christina; Mizi, Athanasia; Georgomanolis, Theodore; Josipovic, Natasa; Gkikas, Dimitrios; Benes, Vladimir; Politis, Panagiotis K.; Papantonis, Argyris; Lygerou, Zoi; Taraviras, Stavros
Abstract
A distinct combination of transcription factors elicits the acquisition of a specific fate and the initiation of a differentiation program. Multiciliated cells (MCCs) are a specialized type of epithelial cells that possess dozens of motile cilia on their apical surface. Defects in cilia function have been associated with ciliopathies that affect many organs, including brain and airway epithelium. Here we show that the geminin coiled-coil domain-containing protein 1 GemC1 (also known as Lynkeas) regulates the transcriptional activation of p73, a transcription factor central to multiciliogenesis. Moreover, we show that GemC1 acts in a trimeric complex with transcription factor E2F5 and tumor protein p73 (officially known as TP73), and that this complex is important for the activation of the p73 promoter. We also provide in vivo evidence that GemC1 is necessary for p73 expression in different multiciliated epithelia. We further show that GemC1 regulates multiciliogenesis through the control of chromatin organization, and the epigenetic marks/tags of p73 and Foxj1. Our results highlight novel signaling cues involved in the commitment program of MCCs across species and tissues. This article has an associated First Person interview with the first author of the paper.
Difficulties with recruiting into neurosurgical clinical trials: The Surgical Trial in IntraCerebral Haemorrhage II as an example
BRITISH JOURNAL OF NEUROSURGERY
Authors: Kirkman, Matthew Anthony; Greenwood, Naomi; Singh, Navneet; Tyrrell, Pippa J.; King, Andrew T.; Patel, Hiren C.
Abstract
Background: Spontaneous supratentorial intracerebral haemorrhage (ICH) is a devastating condition with a high morbidity and mortality, and uncertainty remains regarding the role of surgery in many cases. The Surgical Trial in IntraCerebral Haemorrhage II (STICH II) was initiated to look at subjects with superficial lobar ICH, as the initial STICH trial showed the greatest benefit from early surgery in this subgroup. Our aim was to estimate how many patients with ICH referred to the Greater Manchester Neurosciences Centre (GMNC) met the inclusion and exclusion criteria of the STICH II trial. Methods: The number of patients eligible for STICH II was determined from the GMNC referral database and admissions to the stroke unit over 1 year (2008). Eligibility was determined by predefined criteria, and equipoise was agreed by two consultant neurosurgeons. Results: One hundred and sixty-eight (38.7%) of 434 ICH referrals were lobar ICH; 53 (31.5% of lobar ICH) of these met the radiological and Glasgow Coma Scale (GCS) criteria for STICH II, but only 16 (9.5% of lobar ICH; 3.7% of all ICH) had equipoise agreed on by two neurosurgeons. Thirty-five ICH patients were admitted to the stroke unit, and 12 (34.3%) of these had lobar ICH; none were eligible for STICH II. Conclusions: The number of patients eligible for recruitment into STICH II is small, necessitating an aggressive recruitment approach. Recruitment should focus on neuroscience centres with neurosurgical units as opposed to stroke units.