The clonal origin of the stage 43-44 Xenopus retina from cleavage stage precursors was quantitatively assessed with lineage tracing techniques. The retina descends from a specific subset of those blastomeres that form forebrain. The most animal dorsal midline cell (D1.1.1) produced about half of the retina, the three other dorsal ipsilateral blastomeres each produce about an eighth of the retina, and the four contralateral dorsal blastomeres and an ipsilateral ventral-animal cell together produce the remaining eighth of the retina. There was no significant spatial segregation of the clones derived from different progenitors in either the anterior-posterior or dorsal-ventral axes of the retina and no boundaries between clones were observed. Instead, the clones intermixed to form multiple radial subclones that were equivalent to those demonstrated by marking optic vesicle progenitor cells (Holt et al., 1988; Wetts and Fraser, 1988). This mosaic pattern was initiated by the beginning of gastrulation, advanced in the neural plate, and virtually complete in the optic vesicle. At optic vesicle stages cell movement within subclones was restricted, resulting in the formation of lineally related columns of cells in the mature retina. To determine if the blastomere progenitors are determined to produce these retinal lineage patterns, the major retinal progenitor (D1.1.1) was deleted bilaterally. About 60% of the tadpoles developed normal-appearing eyes; of these the retinas in two-thirds were normal in size and the rest were smaller. The blastomeres surrounding the deleted D1.1.1 progenitors changed their contributions to retina in different ways to effect a complete or partial restoration. Ventral blastomeres, which normally contribute mainly to the tail, produced substantial amounts of the retina while dorsal blastomeres, which normally contribute mainly to the head, decreased their contribution to the retina. To determine whether these changes in retinal lineage were due to changes in blastomere position after the surgery, various other blastomeres were deleted prior to lineage mapping. Dorsal-animal blastomeres took over the retinal fate of their dorsal-vegetal neighbors after those neighbors were deleted, but did not change fate after the deletion of their ventral-animal neighbors. This result suggests that dorsal-animal blastomeres change positional values in only one direction (dorsal to vegetal) after neighbor cell deletion, and that retinal fate is dictated by blastomere position. To test this hypothesis directly, different ventral and vegetal blastomeres, which normally do not produce retina, were transplanted to the position of D1.1.1.(ABSTRACT TRUNCATED AT 400 WORDS)

All mammals must suckle and swallow at birth, and subsequently chew and swallow solid foods, for optimal growth and health. These initially innate behaviors depend critically upon coordinated development of the mouth, tongue, pharynx, and larynx as well as the cranial nerves that control these structures. Disrupted suckling, feeding, and swallowing from birth onward—perinatal dysphagia—is often associated with several neurodevelopmental disorders that subsequently alter complex behaviors. Apparently, a broad range of neurodevelopmental pathologic mechanisms also target oropharyngeal and cranial nerve differentiation. These aberrant mechanisms, including altered patterning, progenitor specification, and neurite growth, prefigure dysphagia and may then compromise circuits for additional behavioral capacities. Thus, perinatal dysphagia may be an early indicator of disrupted genetic and developmental programs that compromise neural circuits and yield a broad range of behavioral deficits in neurodevelopmental disorders.

The average number of primary motoneurons and Rohon-Beard neurons that descend from each "identified" blastomere of the 16- and 32-cell stages of the frog Xenopus laevis was determined. The dorsal, animal blastomeres are the major motoneuron progenitors, and the ventral, animal blastomeres are the major Rohon-Beard progenitors. Cells along the midline primarily give rise to only one of these phenotypes, whereas cells along the frontal plane, which separates dorsal from ventral, give rise to both phenotypes. Each blastomere produces a characteristic number of each type of neuron, with only small variations between embryos. The mean values were used to construct quantitative retrospective lineage diagrams for the first 5 cell cycles after fertilization. These diagrams illustrate that the fate to become a major neuronal progenitor is segregated as early as the 4-cell stage. The lineage patterns of which sister cell makes the majority of primary neurons at each cleavage after the 4-cell stage are quite similar for both neurons in the D lineage but only moderately similar for both neurons in the V lineage. The pattern of predominant Rohon-Beard neuron fate is very similar in the D and V lineages. Analysis of the axial distribution of the primary motoneurons and Rohon-Beard neurons that descend from each blastomere indicates that the major progenitors contribute neuronal descendants periodically, to nearly every segmental bin, but the minor progenitors distribute neuronal descendants randomly along the axis. These data demonstrate that primary neuronal phenotype, cell number, predominant lineal pattern, and in some cases segmental distribution are highly regular across a large population of embryos. This population consistency suggests that several features of neuronal fate may be influenced either by cell position or lineage.

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.