Animal–Vegetal Asymmetries Influence the Earliest Steps in Retina Fate Commitment in Xenopus

Abstract

An individual retina descends from a restricted and invariant group of nine animal blastomeres at the 32-cell stage. We tested which molecular signaling pathways are responsible for the competence of animal blastomeres to contribute to the retina. Inactivation of activin/Vg1 or fibroblast growth factor (FGF) signaling by expression of dominant-negative receptors does not prevent an animal blastomere from contributing to the retina. However, increasing bone morphogenetic protein (BMP) signaling in the retina-producing blastomeres significantly reduces their contribution. Conversely, reducing BMP signaling by expression of a dominant-negative BMP receptor or Noggin allows other animal blastomeres to contribute to the retina. Thus, the initial step in the retinal lineage is regulated by position within the BMP/Noggin field of epidermal versus neural induction. Vegetal tier blastomeres, in contrast, cannot contribute to the retina even when given access to the appropriate position and signaling fields by transplantation to the dorsal animal pole. We tested whether expression of molecules within the mesoderm inducing (activin, FGF), mesoderm-modifying (Wnt), or neural-inducing (BMP, Noggin) pathways impart a retinal fate on vegetal cell descendants. None of these, several of which induce secondary head structures, caused vegetal cells to contribute to retina. This was true even if the injected blastomeres were transplanted to the dorsal animal pole. Two pathways that specifically induce head tissues also were investigated. The simultaneous blockade of Wnt and BMP signaling, which results in the formation of a complete secondary axis with head and eyes, did not cause the vegetal clone to give rise to retina. However, Cerberus, a secreted protein that also induces an ectopic head with eyes, redirected vegetal progeny into the retina. These experiments indicate that vegetal blastomere incompetence to express a retinal fate is not due to a lack of components of known signaling pathways, but relies on a specific pathway of head induction.

Differential role of 14‐3‐3 family members in Xenopus development

“…Previous work demonstrated that the FGF receptor 1 is not required for early Xenopus eye induction or patterning (Kroll and Amaya, 1996), and inactivation of FGF by use of a dominant-negative FGF receptor 1 did not prevent animal blastomeres from contributing to the retina (Moore and Moody, 1999). In contrast, a more recent study in transgenic frogs showed that FGF receptor 4a is required for the correct specification of retinal cell types (Zhang et al, 2003).…”

Generation of Functional Eyes from Pluripotent Cells

“…In Xenopus , Noggin can direct the progeny of early blastomeres, not normally destined to contribute to the eyes, to a retinal fate [19],[20]. Human ES cells treated with Noggin, Dickkopf-1, and Insulin-like Growth Factor-1 proteins differentiate into functional photoreceptors [5].…”

“…Movies were made using this software and exported as QuickTime movies. Eye volumes were calculated by summing the area of every eye section and multiplying by the section thickness (12 µM) as previously described using Volocity Software [19].…”

Fibroblast Growth Factor Receptor-induced Phosphorylation of EphrinB1 Modulates Its Interaction with Dishevelled

“…Vertebrate retinal development consists of a series of steps that progressively restrict the available cell fates, and retinal progenitors need to be positioned within the eye field to receive the local environmental signals that will direct their ultimate fate (Huang and Moody, 1993;Moore and Moody, 1999). The retinal precursor cells that give rise to the vertebrate eye field are specified by several transcription factors that both promote retinal fate and control cell movement of progenitor cells during gastrulation and neurulation (Kenyon et al, 2001).…”