Developmental origins of precocial forelimbs in marsupial neonates.

Marsupial mammals are born in an embryonic state, as compared with their eutherian counterparts, yet certain features are accelerated. The most conspicuous of these features are the precocial forelimbs, which the newborns use to climb unaided from the opening of the birth canal to the teat. The developmental mechanisms that produce this acceleration are unknown. Here we show that heterochronic and heterotopic changes early in limb development contribute to forelimb acceleration. Using Tbx5 and Tbx4 as fore- and hindlimb field markers, respectively, we have found that, compared with mouse, both limb fields arise notably early during opossum development. Patterning of the forelimb buds is also accelerated, as Shh expression appears early relative to the outgrowth of the bud itself. In addition, the forelimb fields and forelimb myocyte allocation are increased in size and number, respectively, and migration of the spinal nerves into the forelimb bud has been modified. This shift in the extent of the forelimb field is accompanied by shifts in Hox gene expression along the anterior-posterior axis. Furthermore, we found that both fore- and hindlimb fields arise gradually during gastrulation and extension of the embryonic axis, in contrast to the appearance of the limb fields in their entirety in all other known cases. Our results show a surprising evolutionary flexibility in the early limb development program of amniotes and rule out the induction of the limb fields by mature structures such as the somites or mesonephros.

Causes of Childhood Blindness in North Ghana: Results From a School for the Blind in Wa, Upper West Region

Background: Because most developing countries lack sufficient resources and infrastructure to conduct population-based studies on childhood blindness, it can be difficult to obtain epidemiologically reliable data available for planning public health strategies to effectively address the major determinants of childhood blindness. The major etiologies of blindness can differ regionally and intra-regionally. The objective of this retrospective study was to determine (1) the major causes of childhood blindness (BL) and severe visual impairment (SVI) in students who attend Wa Methodist School for the Blind in Upper West Region, North Ghana, and (2) any potential temporal trends in the causes of blindness for this region.

Methods: In this retrospective study, demographic data and clinical information from an eye screening at Wa Methodist School for the Blind were coded according to the World Health Organization/Prevention of Blindness standardized reporting methodology. Causes of BL and SVI were categorized anatomically and etiologically. We determined the major causes of BL/SVI over time using information provided about the age at onset of visual loss for each student.

Results: The major anatomical causes of BL/SVI among the 190 students screened were corneal opacity and phthisis bulbi (n=28, 15%), optic atrophy (n=23, 13%), glaucoma (n=18, 9%), microphthalmos (n=18, 9%), and cataract (n=18, 9%). Within the first year of life, students became blind mainly due to whole globe causes (n=23, 26%), cataract (n=15, 17%), and optic atrophy (n=11, 13%). Those who became blind after age one year had whole globe causes (n=26, 26%), corneal opacity (n=24, 24%), and optic atrophy (n=13, 13%).

Conclusion: At the Wa Methodist School for the Blind, the major anatomical causes of BL/SVI were corneal opacity and phthisis bulbi. About half of all students became blind within the first year of life, and were disproportionately affected by cataract and retinal causes in comparison to the other students who became blind after age one year. While research in blind schools has a number of implicit disadvantages and limitations, considering the temporal trends and other epidemiological factors of blindness may increase the usefulness and/or implications of the data that come from blind school studies in order to improve screening methods for newborns in hospitals and primary care centers, and to help tailor preventative and treatment programs to reduce avoidable childhood blindness in neonates and schoolchildren.