Graham A, Koentges G, Lumsden A
Department of Experimental Pathology and, Guys Hospital, London Bridge, London, SE1 9RT, United Kingdom
Mol Cell Neurosci. 1996 Aug;8(2/3):76-83. doi: 10.1006/mcne.1996.0046.
During development of the vertebrate head neural crest cells emigrate from the hindbrain and populate the branchial arches, giving rise to distinct skeletal elements and muscle connective tissues in each arch. The production of neural crest from the hindbrain is discontinuous and crest cells destined for different arches, carrying different positional cues, are separated by regions of apoptosis centered on rhombomeres (r) 3 and r5. This cell death program is under the interactive control of the neighboring hindbrain segments. Both r3 and r5 produce large numbers of crest cells when freed from their flanking rhombomere, but when conjoined with their neighbor the cell death program is restored. Two key components of this program are Bmp 4 and msx-2, both of which are expressed in the apoptotic foci of r3 and r5 and which are also regulated by neighbor interactions. Importantly, the addition of recombinant Bmp 4 to isolated cultures of r3 and r5 induces the expression of Bmp 4 and msx-2 and restores the cell death program. This early neural crest segregation is maintained during development and it has profound effects upon the final craniofacial pattern. Even though crest cells from different axial origins will contribute to compound skeletal elements, these distinct populations do not intermingle. Furthermore head muscle connective tissues are exclusively anchored to skeletal domains arising from neural crest from the same axial level. Thus the discontinuous production of neural crest sculpts the crest into nonmixing streams and consequently ensures the fidelity of patterning.
在脊椎动物头部发育过程中，神经嵴细胞从后脑迁出并填充鳃弓，在每个鳃弓中形成不同的骨骼成分和肌肉结缔组织。后脑产生神经嵴的过程是不连续的，注定要进入不同鳃弓、携带不同位置线索的嵴细胞，被以菱脑节（r）3和r5为中心的凋亡区域分隔开。这种细胞死亡程序受相邻后脑节段的交互控制。当r3和r5从其相邻的菱脑节分离时，它们都会产生大量的嵴细胞，但当与相邻节段相连时，细胞死亡程序就会恢复。该程序的两个关键成分是Bmp 4和msx - 2，它们都在r3和r5的凋亡灶中表达，并且也受相邻节段相互作用的调节。重要的是，向r3和r5的分离培养物中添加重组Bmp 4会诱导Bmp 4和msx - 2的表达，并恢复细胞死亡程序。这种早期神经嵴的分离在发育过程中得以维持，并对最终的颅面模式产生深远影响。尽管来自不同轴向起源的嵴细胞会参与复合骨骼成分的形成，但这些不同的细胞群体不会相互混合。此外，头部肌肉结缔组织仅附着于来自相同轴向水平神经嵴的骨骼区域。因此，神经嵴的不连续产生将嵴塑造成不混合的细胞流，从而确保了模式形成的准确性。
