Intrinsic Bias and Lineage Restriction in the Phenotype Determination of Dopamine and Neuropeptide Y Amacrine Cells

Abstract

Blastomere lineages are differentially biased to produce different neurotransmitter subtypes of amacrine cells (Huang and Moody, 1995, 1997,). To elucidate when this bias is acquired, we examined amacrine lineages at different early developmental times. Our experiments demonstrate that the bias to express dopamine and neuropeptide Y amacrine fates involves several steps before the formation of the definitive optic cup. At cleavage stages, a retinal progenitor that contributes large numbers of cells is already biased to produce its normal repertoire of dopamine amacrine cells, as revealed by transplantation to a new location, whereas the amacrine fate of a progenitor that contributes fewer cells is modified by its new position. At neural plate stages, not all retinal progenitors are multipotent. Nearly one-half populate only the inner nuclear layer and are enriched in amacrine cells. During early optic vesicle stages, an appropriate mitotic tree is required for dopamine and neuropeptide Y, but not serotonin, amacrine cell clusters to form. Thus, the acquisition of amacrine fate bias involves intrinsic maternal factors at cleavage, fate restriction in the neural plate, and specified mitotic patterns in the optic vesicle. At each of these steps only a subset of the embryonic retinal progenitors contributing to amacrine subtypes is biased; the remaining progenitors maintain multipotency. Thus, from the earliest embryonic stages, progenitors of the retina are a dynamic mosaic. This is the first experimental demonstration of amacrine fate decisions that occur during early embryonic periods in advance of the events described in the later, committed retina.

Role of theBarhl2homeobox gene in the specification of glycinergic amacrine cells

“…Barhl2, probably together with Pax6, then promotes the differentiation of glycinergic amacrine cells from faterestricted amacrine progenitors. Such fate-restricted amacrine progenitors have been identified by fate tracing experiments in early rat and Xenopus retinas (Alexiades and Cepko, 1997;Huang and Moody, 1997;Moody et al, 2000). However, it remains to be determined what factors are involved in the differentiation of GABAergic amacrine cells.…”

The role of early lineage in GABAergic and glutamatergic cell fate determination in Xenopus laevis

“…Several other members of the GABA and glutamate transporter families have been reported in mammals, and it remains a possibility that subpopulations within these neurotransmitter phenotypes are biased by early lineage. If different subtypes were produced by different subsets of progenitors, an analysis of the entire class, such as that performed in the current study, would be unable to reveal fate bias (Moody et al, 2000).…”

Molecular regulation of vertebrate retina cell fate

“…1A). Lineage tracing experiments in Xenopus have shown that both the early retinogenic blastomeres and the cells of the eye field are not homogeneous populations, being composed of cells with different potentialities (Moody et al, 2000). For instance, individual retinogenic blastomeres are differentially biased to generate distinct subsets of amacrine cells.…”

“…For instance, individual retinogenic blastomeres are differentially biased to generate distinct subsets of amacrine cells. Similarly, eye field cells can be grouped into two classes: multipotent progenitors that will generate all the retinal cell types and progenitors with a more restricted potential, giving rise to cells of a single retinal layer (Moody et al, 2000). It is unclear whether the mixed cell population of the eye field may reflect the co‐existence of progenitors in two determinative states, displaying progressively restricted potentialities, or, rather, distinct primary and secondary progenitors that will give rise to the larval and the adult retina, respectively.…”