Articles

Diversity and Pattern in the Developing Spinal Cord

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Science  15 Nov 1996:
Vol. 274, Issue 5290, pp. 1115-1123
DOI: 10.1126/science.274.5290.1115

Figures

  • Fig. 1.

    Polarized sources of inductive signals during spinal cord development. (A) Stages in the embryonic development of the spinal cord: The neural plate is generated as a columnar epithelium and is underlain by axial mesoderm cells of the notochord (N), and paraxial mesoderm (later the somites) (S) and is flanked by epidermal ectoderm (ECT). During neurulation, the neural plate buckles at its midline to form the neural folds and a floor plate (F) forms at its midline. The neural tube forms by fusion of the dorsal tips of the neural folds, generating roof plate cells at its dorsal midline and neural crest cells (NC), which emigrate from the dorsal neural tube. Neuroepithelial cells proliferate and differentiate into neurons located at different dorsoventral positions. Subclasses of commissural (C) and association (A) neurons differentiate dorsally, close to the roof plate, whereas motor neurons (M) and ventral interneurons (V) differentiate ventrally near the floor plate. Dorsal root ganglion (DRG) neurons are generated from post-migratory neural crest cells. (B) The diagram shows the source of ventralizing [Sonic Hedgehog (Shh), blue] and dorsalizing (BMPs, orange) inductive signals at sequential stages of spinal cord development. Shh is initially expressed in the axial mesoderm, and BMPs originate in the epidermal ectoderm flanking the lateral edges of the neural plate. At neural fold stages, Shh begins to be expressed by floor plate cells at the midline of the neural plate and BMPs by cells in the dorsal tips of the neural folds. After neural tube closure, BMP expression is lost from the epidermal ectoderm except at the dorsal midline but BMPs are now expressed in the roof plate and adjacent dorsal neural tube. At the onset of neuronal differentiation, BMP expression persists in the dorsal neural tube, and Shh expression is maintained in the floor plate.

  • Fig. 2.

    Mechanisms of neural induction in Xenopus embryos. (A) Ectodermal cells of the animal pole of gastrula-stage Xenopus embryos are subject to tonic BMP4-mediated signaling (red arrows), which promotes their differentiation into epidermal cells. Blockade of BMP4 signaling elicits the formation of anterior neural plate tissue. Exposure of ectoderm to FGFs under conditions in which BMP4 signaling is reduced or eliminated leads to the generation of posterior neural plate tissue. (B) A potential mechanism of action of anterior neural inducers derived from prospective axial mesoderm (the organizer region). Chordin, noggin, and follistatin are each secreted by organizer cells and induce neural tissue by blocking BMP4-mediated signaling between ectodermal cells. RI and RII, BMP receptor subunits. (C) Both noggin and chordin bind to BMP4. Follistatin can bind to BMP7 and possibly also to other BMPs.

  • Fig. 3.

    Pax gene expression during spinal cord development. During the transformation of the neural plate into the neural tube in the chick embryo, the regulated expression of three Pax genes—Pax3, Pax6, and Pax7—subdivides the neural tube into distinct domains. Caudal neural plate cells at all mediolateral positions initially express Pax3 and Pax7. At neural fold stages, Pax3 and Pax7 expression is repressed medially and Pax 6 expression is detected at all mediolateral positions except at the midlines. After neural tube closure, Pax3 and Pax7 expression is restricted to the dorsal half of the neural tube, whereas Pax6 is expressed by more ventral cells. Pax6 is also expressed by cells in the dorsal half of the neural tube. N, notochord, F, floor plate.

  • Fig. 4.

    LIM homeodomain protein expression in motor columns in the chick spinal cord. The temporal sequence of expression of LIM homeodomain proteins by newly differentiating motor neurons. All classes of motor neuron initially express Isl1 and Isl2, soon after their birth. Differential expression of LIM homeodomain proteins occurs at around the time of axon extension. The lower diagram shows transverse sections through stage 22 to 25 chick embryos at different segmental levels, indicating the projection of motor neurons located in different motor columns to their peripheral targets. The medial division of the median motor column is shown in blue (MMCm); the lateral division of the median motor column is shown in red (MMCl); the medial division of the lateral motor column (LMC) in red (LMCm); the lateral division of the LMC in green (LMCl); and the column of Terni in brown (CT).

  • Fig. 5.

    Model for the role of Neurogenin, NeuroD, and Notch signaling in the determination of neuronal fate. The conversion of a neural epithelium consisting exclusively of proliferating progenitor cells (gray) to one in which certain cells have adopted a neuronal identity (green) is shown. The acquisition of neuronal identity requires the action of bHLH proteins and Notch signaling. The model indicates that Neurogenin expression in the left hand cell induces expression of Delta, which in turn activates Notch signaling in the right-hand cell, leading to the repression of Neurogenin expression and consequently to a decrease in Delta expression. By analogy with similar signaling events in Drosophila, the inhibition of Neurogenin expression may be mediated by RBP-Jk, a vertebrate homolog of Suppressor of Hairless [Su(H)] and through HES proteins, vertebrate bHLH proteins of the Hairy/enhancer of split [E(spl)] class (113, 114). Neurogenin expression above a certain threshold leads to the induction of NeuroD, which promotes neuronal differentiation. Modified with permission from (93).

  • Fig. 6.

    Dorsoventral subdivisions of the ventricular zone of the developing spinal cord and early neuronal patterning. At the onset of neuronal differentiation, the ventricular zone of the embryonic spinal cord is subdivided into dorsoventral domains that express different combinations of bHLH proteins, Notch ligands, and Pax proteins. The right-hand diagram shows that subsets of neurons derived from different domains of the ventricular zone can be distinguished by the expression of LIM homeodomain proteins. Motor neurons (red) express Isl1/Isl2, certain dorsal commissural neurons (green) express LH2a/LH2b; and dorsal ipsilateral interneurons (orange) express Isl1. The axonal projection patterns of the remaining interneuron classes have not been established. Motor neurons can be further subdivided into columnar subsets on the basis of a more complex LIM homeodomain protein code (see Fig. 4).

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