Establishment of a ventral cell fate in the spinal cord

Abstract

The neural plate is induced during gastrulation when the organizer affects the ectoderm around it. Recent experiments show that axial mesoderm can stimulate formation of specific ventral cell types in the spinal cord, including floor plate, motor neurons, and several types of interneurons. We have eliminated or disrupted axial mesoderm by using a variety of methods to show that ventral columns of intermittent dopaminergic neurons in the frog Xenopus also appear to be induced by axial mesoderm. Inversion of the dorsal-ventral neural axis by splitting the presumptive neural plate in vivo, produced two spinal cords with ectopic dopaminergic neurons. The location and number of neurons suggest that even a brief association with axial mesoderm can specify the identity of the first or primary dopaminergic neurons and that notochord retains the ability to induce cells to become secondary dopaminergic neurons. Developmental Dynamics 227:552-562, 2003.

Activated Notch Disrupts the Initial Patterning of Dopaminergic Spinal Cord Neurons

“…These results show that secondary neuron production was unaffected and that secondary neuron precursors did not regulate for missing primary neurons. Secondary dopaminergic neurons can be induced separately from primary dopaminergic neurons and can even be induced from cells that orig-inated in the lateral (dorsal) columns of the neural plate [Moghadam et al, 2003]. The precursors to these ectopic secondary neurons had no relationship to the primary dopaminergic neuron precursors or their pattern.…”

“…Motor neurons also come from these columns while Rohon Beard neurons originate from the two lateral columns. During normal development, Notch and Delta are expressed in all three pairs of spinal cord columns starting at the end of gastrulation (0.55 days, stage 12) in the presumptive neural plate , which is close to the time (0.5 days, stage 11) that the ventral identity of spinal cord cells is established [Moghadam et al, 2003]. If the activated form of Notch is overexpressed, there are fewer N-tubulin positive cells in all neural plate columns , and if overexpression is maintained, few neurons differentiate in any part of the developing spinal cord [Park and Appel, 2003].…”

“…Recent work showed that primary dopaminergic neurons did not need to be present for secondary neuron induction [Moghadam et al, 2003]. Since activated Notch RNA and protein are short-lived [see Scheer et al, 2001 for data on zebrafi sh], we hypothesized that overexpression should have the greatest effect on the differentiation of primary neurons.…”

“…They are located in two longitudinal columns in the ventral spinal cord where they assume a nonrandom dispersed pattern [Heathcote and Chen, 1993], which is consistent with a pattern formed by a lateral inhibitory mechanism. The fate of the fi rst or primary dopaminergic neurons can be established as early as mid-gastrulation (0.5 days or stage 11) [Moghadam et al, 2003], and they continue to differentiate for weeks throughout embryonic larval and metamorphic development [Heathcote and Chen, 1994]. We overexpressed an activated form of Notch well before mid-gastrulation by injecting RNA encoding Xotch ⌬ E [Coffman et al, 1993] into one cell at the two-cell stage of development ( fi g. 1 A).…”

“…Notch signaling during the early stages of nervous system development leads to a reduction in the number of cells expressing a neural specifi c form of tubulin (primary neurons) in all three pairs of longitudinal columns in the neural plate . Previous experiments have shown that the fi rst or primary dopaminergic spinal cord neurons are induced during midgastrulation (0.5 days or stage 11) [Moghadam et al, 2003], which is close to the time that Notch is expressed in the presumptive neural plate (0.55 days or stage 12) . The close temporal correlation between primary dopaminergic cell induction and the onset of Notch expression in addition to the distinctive pattern of dopaminergic cells throughout embryonic and larval development, led us to test whether Notch activation could infl uence the differentiation of this specifi c class of central neuron.…”