Defining intermediate stages in cell determination: Acquisition of a lens‐forming bias in head ectoderm during lens determination

Abstract

Cell determination in vertebrates requires integration of many events, although the mechanisms controlling the different stages in this process are poorly understood. While studies of lens determination have helped define some of these stages, we know very little about the intermediate steps involved in the commitment of ectoderm to lens formation. Lens determination begins during gastrulation when ectoderm is briefly competent to respond to lens-inducing signals and progresses to a point, at the neural tube stage, when the presumptive lens ectoderm is specified. Between these two stages important regulatory genes are activated in the presumptive lens ectoderm, including the transcription factor Pax-6, and transplantation experiments presented here suggest that the presumptive lens ectoderm is becoming "biased" toward lens formation. We show that competent ectoderm from Xenopus laevis embryos forms well-differentiated lenses in most cases when transplanted to the presumptive lens area of neural plate stage hosts, where the lens-inductive environment is strong. When placed into later, neural tube stage hosts, optimally competent ectoderm does form small lenses in about half the cases, but the overall response is much weaker. Even in this weakly inducing environment, however, lens ectoderm that is part way through the inductive process (at the neural plate stage) is shown to have a lens-forming bias, since it forms well differentiated lenses in nearly all cases. While we find that ectoderm surrounding the lens-forming area at neural plate stages does not have a lens-forming bias, non-lens head ectoderm at the neural tube stage does, suggesting that a large region of head ectoderm is biased during neurulation. Using Rana palustris embryos, a species used in the earliest lens induction studies, we were also able to show that the optic vesicle can induce lenses in non-lens head ectoderm at neural tube stages. These results lead us to refine the definition of lens cell determination and provide a context that should allow clarification of determination mechanisms.

The lens‐regenerating competence in the outer cornea and epidermis of larval Xenopus laevis is related to pax6 expression

“…Many studies on Xenopus laevis embryo have defined steps in lens formation during eye development (Henry & Grainger, 1990;Servetnick & Grainger, 1991;Grainger, 1992;Grainger et al 1997). The early phase begins at the mid-gastrula stage when the ectoderm becomes competent to respond to lens-inductive signals.…”

The lens equator: A platform for molecular machinery that regulates the switch from cell proliferation to differentiation in the vertebrate lens

“…Third, the lens placode is specified when the presumptive retina is located close to the presumptive lens ectoderm. Fourth, lens cells start to differentiate into lens fiber cells (Grainger et al 1997). Recently it has been reported that competence of lens formation in the head ectoderm is not only promoted by signals from the anterior neural plate, but is also restricted by transforming growth factor-b (TGF-b) and canonical Wnt signaling from neural crest cells (Grocott et al 2010), suggesting that lens placode induction is cooperatively regulated by positive and negative signals.…”

Defining progressive stages in the commitment process leading to embryonic lens formation

“…We have been examining these issues during the development of the amphibian embryonic lens where, in contrast to many other model organisms, it is feasible to examine all stages of development, and to readily study developmental commitment in cultured tissues or in transplants (Grainger, 1992;Grainger et al, 1997). We have described a sequence of events in lens formation that serves as a framework for the studies presented here.…”