Hunt P, Clarke J D, Buxton P, Ferretti P, Thorogood P
Developmental Biology Unit, Institute of Child Health, London, United Kingdom.
Dev Biol. 1998 Jun 1;198(1):82-104. doi: 10.1006/dbio.1998.8886.
The extent to which the spatial organisation of craniofacial development is due to intrinsic properties of the neural crest is at present unclear. There is some experimental evidence supporting the concept of a prepattern established within crest while contiguous with the neural plate. In experiments in which the neural tube and premigratory crest are relocated within the branchial region, crest cells retain patterns of gene expression appropriate for their position of origin after migration into the branchial arches, resulting in skeletal abnormalities. But in apparent conflict with these findings, when crest is rerouted by late deletion of adjacent crest, infilling crest alters its pattern of gene expression to match its new location, and a normal facial skeleton results. In order to reconcile these findings thus identify processes of relevance to the course of normal development, we have performed a series of neural tube and crest rotations producing a more extensive reorganisation of cephalic crest than has been previously described. Lineage analysis using DiI labelling of crest derived from the rotated hindbrain reveals that crest does not migrate into the branchial arch it would have colonised in normal development, rather it simply populates the nearest available branchial arches. We also find that crest adjacent to the grafted region contributes to a greater number of branchial arches than it would in normal development, resulting in branchial arches containing mixed cell populations not occurring in normal development. We find that after exchange of first and third arch crest by rotation of r1-7, crest alters its expression of hoxa-2 and hoxa-3 to match its new location within the embryo resulting in the reestablishment of the normal branchial arch Hox code. A facial skeleton in which all the normal components are present, with some additional ectopic first arch structures, is formed in this situation. In contrast, when second and third arch crest are exchanged by rotation of r3 to 7, ectopic Hox gene expression is stable, resulting in the persistence of an abnormal branchial arch Hox code and extensive defects in the hyoid skeleton. We suggest that the intrinsic properties of crest have an effect on the spatial organisation of structures derived from the branchial arches, but that exposure to increasingly novel environments within the branchial region or "community effects" within mixed populations of cells can result in alterations to crest Hox code and morphogenetic fate. In both classes of operation we find that there is a tight link between the resulting branchial arch Hox code and a particular skeletal morphology.
目前尚不清楚颅面发育的空间组织在多大程度上归因于神经嵴的内在特性。有一些实验证据支持在神经嵴与神经板相邻时在其中建立预模式的概念。在将神经管和迁移前的神经嵴重新定位到鳃区的实验中，神经嵴细胞在迁移到鳃弓后保留与其起源位置相适应的基因表达模式，从而导致骨骼异常。但与这些发现明显矛盾的是，当通过后期删除相邻神经嵴来重新引导神经嵴时，填充进来的神经嵴会改变其基因表达模式以匹配其新位置，从而形成正常的面部骨骼。为了调和这些发现并确定与正常发育过程相关的过程，我们进行了一系列神经管和神经嵴旋转操作，产生了比先前描述的更广泛的头部神经嵴重组。使用DiI标记来自旋转后脑的神经嵴进行谱系分析表明，神经嵴不会迁移到正常发育中它会定植的鳃弓，而是简单地填充最近的可用鳃弓。我们还发现，移植区域附近的神经嵴在正常发育中比正常情况下对更多的鳃弓有贡献，导致鳃弓中含有正常发育中不会出现的混合细胞群。我们发现，通过r1 - 7的旋转交换第一和第三鳃弓神经嵴后，神经嵴会改变其hoxa - 2和hoxa - 3的表达以匹配其在胚胎内的新位置，从而重新建立正常的鳃弓Hox编码。在这种情况下会形成一个面部骨骼，其中所有正常成分都存在，还有一些额外的异位第一鳃弓结构。相反，当通过r3到7的旋转交换第二和第三鳃弓神经嵴时，异位Hox基因表达是稳定的，导致异常的鳃弓Hox编码持续存在以及舌骨骨骼出现广泛缺陷。我们认为神经嵴的内在特性对源自鳃弓的结构的空间组织有影响，但在鳃区内暴露于越来越新颖的环境或细胞混合群体中的“群体效应”可导致神经嵴Hox编码和形态发生命运的改变。在这两类操作中，我们都发现所产生的鳃弓Hox编码与特定的骨骼形态之间存在紧密联系。
