Sela-Donenfeld Dalit, Kayam Galya, Wilkinson David G
Koret School of Veterinary Medicine, The Hebrew University, The Robert H Smith Faculty of Agriculture, Food and Environment, Rehovot, Israel.
BMC Dev Biol. 2009 Feb 20;9:16. doi: 10.1186/1471-213X-9-16.
During formation of the vertebrate central nervous system, the hindbrain is organized into segmental units, called rhombomeres (r). These cell-lineage restricted segments are separated by a subpopulation of cells known as boundary cells. Boundary cells display distinct molecular and cellular properties such as an elongated shape, enriched extracellular matrix components and a reduced proliferation rate compared to intra-rhombomeric cells. However, little is known regarding their functions and the mechanisms that regulate their formation.
Hindbrain boundary cells express several signaling molecules, such as FGF3, which at earlier developmental stages is transiently expressed in specific rhombomeres. We show that chick embryos that lack boundary cells due to overexpression of truncated EphA4 receptor in the hindbrain have continued segmental expression of FGF3 at stages when it is normally restricted to hindbrain boundaries. Furthermore, surgical ablation of the boundary between r3 and r4, or blocking of the contact of r4 with boundary cells, results in sustained FGF3 expression in this segment.
These findings suggest that boundary cells are required for the downregulation of segmental FGF3, presumably mediated by a soluble factor(s) that emanates from boundaries. We propose that this new function of boundary cells enables a switch in gene expression that may be required for stage-specific functions of FGF3 in the developing hindbrain.
在脊椎动物中枢神经系统形成过程中，后脑被组织成称为菱脑节（r）的节段单元。这些细胞谱系受限的节段由称为边界细胞的细胞亚群分隔。与菱脑节内细胞相比，边界细胞表现出独特的分子和细胞特性，如细长的形状、丰富的细胞外基质成分和较低的增殖率。然而，关于它们的功能以及调节其形成的机制知之甚少。
后脑边界细胞表达几种信号分子，如FGF3，在早期发育阶段它在特定菱脑节中短暂表达。我们发现，由于后脑截断的EphA4受体过表达而缺乏边界细胞的鸡胚，在FGF3正常局限于后脑边界的阶段，其在节段中的表达仍持续存在。此外，手术切除r3和r4之间的边界，或阻断r4与边界细胞的接触，会导致该节段中FGF3持续表达。
这些发现表明边界细胞是节段性FGF3下调所必需的，推测是由边界产生的一种或多种可溶性因子介导的。我们提出，边界细胞的这种新功能能够实现基因表达的转换，这可能是FGF3在发育中的后脑中发挥阶段特异性功能所必需的。
