Graduate School of Medicine, Korea University, Ansan, Gyeonggido 425-707, Republic of Korea.
J Neurosci. 2013 Jan 23;33(4):1728-33. doi: 10.1523/JNEUROSCI.3369-12.2013.
A subset of ventral spinal cord precursors, known as pMN precursor cells, initially generate motor neurons and then oligodendrocyte progenitor cells (OPCs), which migrate and differentiate as myelinating oligodendrocytes in the developing neural tube. The switch between motor neuron and oligodendrocyte production by the pMN neural precursors is an important step in building a functional nervous system. However, the precise mechanism that orchestrates the sequential generation of motor neurons and oligodendrocytes within the common population of pMN precursors is still unclear. The current study demonstrates that Indian Hedgehog b (Ihhb), previously known as Echidna Hedgehog, begins to be expressed in the floor plate cells of the ventral spinal cord at the time of OPC specification in zebrafish embryos. Ihhb loss-of-function analysis revealed that Ihhb function is required for OPC specification from pMN precursors by negatively regulating the proliferation of neural precursors. Finally, results showed that Sonic Hedgehog (Shh) could not replace Ihhb function in OPC specification, suggesting that Ihhb and Shh play separate roles in OPC specification. Altogether, data from the present study suggested a novel mechanism, mediated by Ihhb, for the sequential generation of motor neurons and oligodendrocytes from pMN precursors in the ventral spinal cord of zebrafish embryos.
一组腹侧脊髓前体细胞，称为 pMN 前体细胞，最初产生运动神经元，然后产生少突胶质前体细胞（OPC），这些细胞在发育中的神经管中迁移并分化为髓鞘形成的少突胶质细胞。pMN 神经前体细胞中运动神经元和少突胶质细胞产生的转换是构建功能神经系统的重要步骤。然而，协调 pMN 前体细胞中运动神经元和少突胶质细胞顺序产生的精确机制仍不清楚。本研究表明，先前称为 Hedgehog 蛋白（Echidna Hedgehog）的印度刺猬素 b（Ihhb）在斑马鱼胚胎 OPC 特化时开始在腹侧脊髓的基板细胞中表达。Ihhb 功能丧失分析表明，Ihhb 功能通过负向调节神经前体细胞的增殖来调控 pMN 前体细胞中 OPC 的特化。最后，结果表明 Sonic Hedgehog（Shh）不能替代 Ihhb 在 OPC 特化中的功能，表明 Ihhb 和 Shh 在 OPC 特化中发挥着不同的作用。总的来说，本研究的数据表明，在斑马鱼胚胎腹侧脊髓中，pMN 前体细胞中运动神经元和少突胶质细胞的顺序产生是由 Ihhb 介导的一种新机制。
