Gaufo Gary O, Wu Sen, Capecchi Mario R
Howard Hughes Medical Institute, Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
Development. 2004 Mar;131(6):1259-66. doi: 10.1242/dev.01029. Epub 2004 Feb 11.
The perception of environmental stimuli is mediated through a diverse group of first-order sensory relay interneurons located in stereotypic positions along the dorsoventral (DV) axis of the neural tube. These interneurons form contiguous columns along the anteroposterior (AP) axis. Like neural crest cells and motoneurons, first-order sensory relay interneurons also require specification along the AP axis. Hox genes are prime candidates for providing this information. In support of this hypothesis, we show that distinct combinations of Hox genes in rhombomeres (r) 4 and 5 of the hindbrain are required for the generation of precursors for visceral sensory interneurons. As Hoxa2 is the only Hox gene expressed in the anterior hindbrain (r2), disruption of this gene allowed us to also demonstrate that the precursors for somatic sensory interneurons are under the control of Hox genes. Surprisingly, the Hox genes examined are not required for the generation of proprioceptive sensory interneurons. Furthermore, the persistence of some normal rhombomere characteristics in Hox mutant embryos suggests that the loss of visceral and somatic sensory interneurons cannot be explained solely by changes in rhombomere identity. Hox genes may thus directly regulate the specification of distinct first-order sensory relay interneurons within individual rhombomeres. More generally, these findings contribute to our understanding of how Hox genes specifically control cellular diversity in the developing organism
对环境刺激的感知是通过位于神经管背腹（DV）轴上固定位置的多种一级感觉中继中间神经元介导的。这些中间神经元沿前后（AP）轴形成连续的柱。与神经嵴细胞和运动神经元一样，一级感觉中继中间神经元也需要沿AP轴进行特化。Hox基因是提供此信息的主要候选基因。为支持这一假设，我们表明，后脑菱脑节（r）4和5中Hox基因的不同组合是内脏感觉中间神经元前体产生所必需的。由于Hoxa2是在前脑（r2）中表达的唯一Hox基因，该基因的破坏使我们还能够证明躯体感觉中间神经元的前体受Hox基因的控制。令人惊讶的是，所检测的Hox基因对于本体感觉中间神经元的产生并非必需。此外，Hox突变胚胎中一些正常菱脑节特征的持续存在表明，内脏和躯体感觉中间神经元的缺失不能仅通过菱脑节身份的变化来解释。因此，Hox基因可能直接调节单个菱脑节内不同一级感觉中继中间神经元的特化。更一般地说，这些发现有助于我们理解Hox基因如何具体控制发育中生物体的细胞多样性。
