Neuroretina specification in mouse embryos requires Six3-mediated suppression of Wnt8b in the anterior neural plate.

Retinal degeneration causes vision impairment and blindness in humans. If one day we are to harness the potential of stem cell-based cell replacement therapies to treat these conditions, it is imperative that we better understand normal retina development. Currently, the genes and mechanisms that regulate the specification of the neuroretina during vertebrate eye development remain unknown. Here, we identify sine oculis-related homeobox 3 (Six3) as a crucial player in this process in mice. In Six3 conditional-mutant mouse embryos, specification of the neuroretina was abrogated, but that of the retinal pigmented epithelium was normal. Conditional deletion of Six3 did not affect the initial development of the optic vesicle but did arrest subsequent neuroretina specification. Ectopic rostral expansion of Wnt8b expression was the major response to Six3 deletion and the leading cause for the specific lack of neuroretina, as ectopic Wnt8b expression in transgenic embryos was sufficient to suppress neuroretina specification. Using chromatin immunoprecipitation assays, we identified Six3-responsive elements in the Wnt8b locus and demonstrated that Six3 directly repressed Wnt8b expression in vivo. Our findings provide a molecular framework to the program leading to neuroretina differentiation and may be relevant for the development of novel strategies aimed at characterizing and eventually treating different abnormalities in eye formation.

DISCHARGE PLANNING: A PROCESS MODEL

As the requirements for health care hospitalization have become more demanding, so has the discharge planning process become a more important part of the health services system. A thorough understanding of hospital discharge planning can, then, contribute to our understanding of the health services system. This study involved the development of a process model of discharge planning from hospitals. Model building involved the identification of factors used by discharge planners to develop aftercare plans, and the specification of the roles of these factors in the development of the discharge plan. The factors in the model were concatenated in 16 discrete decision sequences, each of which produced an aftercare plan.^ The sample for this study comprised 407 inpatients admitted to the M. D. Anderson Hospital and Tumor Institution at Houston, Texas, who were discharged to any site within Texas during a 15 day period. Allogeneic bone marrow donors were excluded from the sample. The factors considered in the development of discharge plans were recorded by discharge planners and were used to develop the model. Data analysis consisted of sorting the discharge plans using the plan development factors until for some combination and sequence of factors all patients were discharged to a single site. The arrangement of factors that led to that aftercare plan became a decision sequence in the model.^ The model constructs the same discharge plans as those developed by hospital staff for every patient in the study. Tests of the validity of the model should be extended to other patients at the MDAH, to other cancer hospitals, and to other inpatient services. Revisions of the model based on these tests should be of value in the management of discharge planning services and in the design and development of comprehensive community health services.^