GATA Factors Regulate Inner Ear Development and Midbrain Neurogenesis

The zinc-finger transcription factors GATA2 and GATA3 in vertebrates belong to the six-member family that are essential regulators in the development of various organs. The aim of this study was to gain new information of the roles of GATA2 and GATA3 in inner ear morphogenesis and of the function of GATA2 in neuronal fate specification in the midbrain using genetically modified mouse and chicken embryos as models. A century ago the stepwise process of inner ear epithelial morphogenesis was described, but the molecular players regulating the cellular differentiation of the otic epithelium are still not fully resolved. This study provided novel data on GATA factor roles in several developmental processes during otic development. The expression analysis in chicken suggested that GATA2 and GATA3 possess redundant roles during otic cup and vesicle formation, but complementary cell-type specific functions during vestibular and cochlear morphogenesis. The comparative analysis between mouse and chicken Gata2 and Gata3 expression revealed many conserved aspects, especially during later stages of inner ear development, while the expression was more divergent at early stages. Namely, expression of both Gata genes was initiated earlier in chicken than mouse otic epithelium relative to the morphogenetic stages. Likewise, important differences concerning Gata3 expression in the otic cup epithelium were detected between mouse and chicken, suggesting that distinct molecular mechanisms regulate otic vesicle closure in different vertebrate species. Temporally distinct Gata2 and Gata3 expression was also found during otic ganglion formation in mouse and chicken. Targeted inactivation of Gata3 in mouse embryos caused aberrant morphology of the otic vesicle that in severe cases was disrupted into two parts, a dorsal and a ventral vesicle. Detailed analyses of Gata3 mutant embryos unveiled a crucial role for GATA3 in the initial inner ear morphogenetic event, the invagination of the otic placode. A large-scale comparative expression analysis suggested that GATA3 could control cell adhesion and motility in otic epithelium, which could be important for early morphogenesis. GATA3 was also identified as the first factor to directly regulate Fgf10 expression in the otic epithelium and could thus influence the development of the semicircular ducts. Despite the serious problems in the early inner ear development, the otic sensory fate establishment and some vestibular hair cell differentiation was observable in pharmacologically rescued Gata3-/- embryos. Cochlear sensory differentiation was, however, completely blocked so that no auditory hair cells were detected. In contrast to the early morphogenetic phenotype in Gata3-/- mutants, conditional inactivation of Gata2 in mouse embryos resulted in a relatively late growth defect of the three semicircular ducts. GATA2 was required for the proliferation of the vestibular nonsensory epithelium to support growing of the three ducts. Concurrently, with the role in epithelial semicircular ducts, GATA2 was also required for the mesenchymal cell clearance from the vestibular perilymphatic region between the membranous labyrinth and bony capsule. The gamma-aminobutyric acid-secreting (GABAergic) neurons in the midbrain are clinically relevant since they contribute to fear, anxiety, and addiction regulation. The molecular mechanisms regulating the GABAergic neuronal development, however, are largely unknown. Using tissue-specific mutagenesis in mice, GATA2 was characterized as a critical determinant of the GABAergic neuronal fate in the midbrain. In Gata2-deficient mouse midbrain, GABAergic neurons were not produced, instead the Gata2-mutant cells acquired a glutamatergic neuronal phenotype. Gain-of-function experiments in chicken also revealed that GATA2 was sufficient to induce GABAergic differentiation in the midbrain.

Tutkimuksia jätevesilietteen kunnostuksesta ja koneellisesta kuivauksesta

Engl. summary: Studies on conditioning and mechanical dewatering of waste water sludge

Tietokone ikäihmisen arjessa

The aged people in the target group of my study belong to generation, which has experienced the shift from agricultural society via industrial society up to the society which has been described as information society. They have grown up concurrently with the technological development, but during the recent years the technological development has accelerated. One can say that the older the target study group has come the more information technological skills they need to possess to be equal actors in our society. However, especially in case of aged people the learning and maintaining of skills in information technology has mainly been left dependent on their personal motivation. The purpose of this report is to study the use of computers in the life of the aged people. The report studies the will and ability of the aged people to learn the skill of using computers, and the new possibilities which this brings into their lives. The study questions are the following: 1) Why the aged people start to use computers? 2) How the aged people benefit information technology in their own life? 3) How computers have extended the environment of the aged people? 4) What kind of problems the aged people have experienced in use of computers? The research material consists of group interviews and individual interviews (total of 23 people). The interview material has been collected among the participants on information technology courses of the Senior University of Helsinki University during years 2004-2005. The research method used is theme interviewing. In addition, the material of opinions about information technology of people born in decades of 1920 and 1930, gathered as part of the Ikihyvä Päijät-Häme 2002 -research has been used. On basis of this research one can say that the aged people do have motivation to study the use of computers, although many interviewees commented that they also have met problems in use of computers. The motivation has grown also because the fear that without the skills to use computers they could drift into outsiders of the society, whereas instead as skilled computer users they felt to be equal citizens compared with the younger age groups, and that they can maintain their independence and autonomy. Especially, the independent use of banking routines over the Internet and use of emails seem to give them a position as modern actors. Many interview statements also underline that computers will bring both joy and benefit to the users. Studying the use of computers is a new and interesting hobby, which can fill the hole left in the life after leaving the working life. Using skills of text processing and processing of pictures one can, for example, record the traditional knowledge of the family and ancestry to the younger generations, and write articles or even books on the professional area of ones own. Single people emphasize that computers can even act as companionship substitutes. One can use Internet for virtual traveling, which provides a new dimension in use of computers. Internet can also be used to maintain family relationships, especially between grandparents and remote grandchildren. Typical problems in use of computers appeared to be that reaching the right professional helpdesk advisers of the service providers is difficult and requires lots of time and patience. However, the interviewees were not willing to give up their computers, because they had already used to these. Keywords: digital divide, aging, Internet, usability, motivation, information technology, information society.