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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2010.06.025 Byline: Daisuke Kawauchi, Yuko Muroyama, Tatsuya Sato, Tetsuichiro Saito Keywords: Spinal cord; Commissural neuron; Guidance receptor; Bar-class homeobox; LIM homeobox; In vivo electroporation Abstract: During development, commissural neurons in the spinal cord project their axons across the ventral midline, floor plate, via multiple interactions among temporally controlled molecular guidance cues and receptors. The transcriptional regulation of commissural axon-associated receptors, however, is not well characterized. Spinal dorsal cells are transfated into commissural neurons by misexpression of Mbh1, a Bar-class homeobox gene. We examined the function of another Bar-class homeobox gene, Mbh2, and how Mbh1 and Mbh2 modulate expression of the receptors, leading to midline crossing of axons. Misexpression of Mbh1 and Mbh2 showed the same effects in the spinal cord. The competence of spinal dorsal cells to become commissural neurons was dependent on the embryonic stage, during which misexpression of the Mbh genes was able to activate guidance receptor genes such as Rig1 and Nrp2. Misexpression of Lhx2, which has been recently shown to be involved in Rig1 expression, activated Rig1 but not Nrp2, and was less effective in generating commissural neurons. Moreover, expression of Lhx2 was activated by and required the Mbh genes. These findings have revealed a transcriptional cascade, in which Lhx2-dependent and -independent pathways leading to expression of guidance receptors branch downstream of the Mbh genes. Author Affiliation: Department of Developmental Biology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan Article History: Received 15 September 2009; Revised 17 June 2010; Accepted 17 June 2010

Author(s): Yuko Muroyama [1, 4]; Yuko Fujiwara [2]; Stuart H. Orkin (corresponding author) [1, 2]; David H. Rowitch (corresponding author) [1, 3] Astrocytes are the most abundant and functionally diverse [...]

During spinal cord development, oligodendrocytes are generated from a restricted region of the ventral ventricular zone and then spread out into the entire spinal cord. These events are controlled by graded inductive and repressive signals derived from a local organizing center. Sonic hedgehog was identified as an essential ventral factor for oligodendrocyte lineage specification, whereas the dorsal cue was less clear. In this study, Wnt proteins were identified as the dorsal factors that directly inhibit oligodendrocyte development. Wnt signaling through a canonical [beta]-catenin pathway prevents its differentiation from progenitor to an immature state. Addition of rmFz-8/Fc, a Wnt antagonist, increased the number of immature oligodendrocytes in the spinal cord explant culture, demonstrating that endogenous Wnt signaling controls oligodendrocyte development. Keywords: Oligodendrocyte; Wnt; Dorsal factor; Canonical Wnt/[beta]-catenin pathway; Glial differentiation; Sonic hedgehog

Research has been conducted on the dorsal interneurons. Results indicate that the absence of Wnt1 and Wnt3a leads to the diminished development of the dorsal interneurons.

During development of the vertebrate central nervous system (CNS), highly proliferative cells in the ventricular zone of the neural tube serve themselves as progenitors of the various types of neurons, such as interneurons and motor neurons. In the dorsal half of the spinal cord, signals from the roof plate are required for the development of three classes of dorsal interneuron; D1, D2 and D3, listed from dorsal to ventral. This study demonstrates that mouse embryos lacking both Wnt-1 and Wnt-3a are indeed defective in determination of dorsal interneurons. Generation of D1 and D2 classes of dorsal interneurons is impaired; this loss of the dorsal interneurons is compensated by a dorsal expansion of D3 interneuron populations. Most importantly, expression of BMP family proteins, which have been reported to be able to induce dorsal interneurons, is not significantly affected in these mutant embryos. Moreover, the induction of D1 and D2 class interneurons by Wnt-3a protein in the isolated medial region of chick neural plate is demonstrated. Together, these observations clearly indicate that Wnt signaling has a critical role in the generation of D1 and D2 dorsal interneurons.