Hierarchical patterning modes orchestrate hair follicle morphogenesis.
Hierarchical patterning modes orchestrate hair follicle morphogenesis.
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分层图案模式编排毛囊形态发生。
DOI：
10.1371/journal.pbio.2002117
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发表时间：
2017-07
期刊：
影响因子：
9.8
通讯作者：
Headon DJ
中科院分区：
文献类型：
--
作者：
Glover JD;Wells KL;Matthäus F;Painter KJ;Ho W;Riddell J;Johansson JA;Ford MJ;Jahoda CAB;Klika V;Mort RL;Headon DJ
有两种理论阐述了发育过程中重复模式的起源，如毛囊、四肢指甲和肠道绒毛。图灵反应-扩散系统假定，由静态细胞产生的相互作用的可扩散信号首先定义一个预模式，然后该预模式诱导细胞重排以产生解剖结构。第二种理论是间充质自组织理论，它提出移动细胞可以直接形成细胞聚集体的周期模式，而不需要参考任何预先模式。早期毛囊发育的特征是在表皮中迅速出现周期性的基因表达改变的排列，并显著聚集相邻的真皮间充质细胞。我们评估了反应-扩散和间质自组织过程在毛囊模式形成中的贡献和相互作用，确定了一个由成纤维细胞生长因子(FGF)、无翼相关整合位点(WNT)和骨形态发生蛋白(BMP)信号相互作用组成的网络，能够自发地产生周期性模式。利用延时成像，我们发现毛囊上的间充质细胞凝聚是由表皮前图案局部引导的。然而，在整个皮肤上施加高成纤维细胞生长因子和低骨形成蛋白活性的预模式条件，揭示了在没有上皮方向的情况下进行空间模式自组织的潜在真皮能力。这种间充质自组织依赖于限制性的转化生长因子β信号，当反应-扩散模式被抑制时，该信号用于驱动趋化间质模式，但在正常情况下，促进细胞向局部预先图案化的成纤维细胞生长因子来源移动。这项工作说明了在器官发生中运行的周期性构图模式的层次结构。重复的解剖单位形成了一个图案，存在于身体的不同部位。这在皮肤中尤其明显，许多毛囊在胚胎中以均匀分布的斑点的形式规则地排列和固定在适当的位置。这种重复模式的形成基础吸引了许多理论解释。一种有影响力的理论是，细胞首先向彼此发出化学信号，以产生图案的地图，然后按照图案组装一个结构，如毛囊。相反，另一种理论认为，细胞直接聚集在一起，而不是参考预先存在的图谱，以驱动模式的形成。在这项研究中，我们发现一组已知对早期毛囊形成重要的化学信号形成了一个网络，能够产生一个图案化的模板，细胞随后根据其指令移动对该模板做出反应。这支持了基于信号的图案形成理论。然而，引人注目的是，通过在整个皮肤上均匀地施加初始毛囊的条件，我们揭示了皮肤细胞也可以通过结合直接形成模式，而不需要从预先存在的模式中获得指令。然而，细胞直接形成图案的这种能力通常从属于它们遵循由化学信号定义的快速形成的图案模板。这项工作强调，不同的生物模式制作方法可以共存于同一个胚胎器官中，但通常一种方法从属于另一种。
Two theories address the origin of repeating patterns, such as hair follicles, limb digits, and intestinal villi, during development. The Turing reaction–diffusion system posits that interacting diffusible signals produced by static cells first define a prepattern that then induces cell rearrangements to produce an anatomical structure. The second theory, that of mesenchymal self-organisation, proposes that mobile cells can form periodic patterns of cell aggregates directly, without reference to any prepattern. Early hair follicle development is characterised by the rapid appearance of periodic arrangements of altered gene expression in the epidermis and prominent clustering of the adjacent dermal mesenchymal cells. We assess the contributions and interplay between reaction–diffusion and mesenchymal self-organisation processes in hair follicle patterning, identifying a network of fibroblast growth factor (FGF), wingless-related integration site (WNT), and bone morphogenetic protein (BMP) signalling interactions capable of spontaneously producing a periodic pattern. Using time-lapse imaging, we find that mesenchymal cell condensation at hair follicles is locally directed by an epidermal prepattern. However, imposing this prepattern’s condition of high FGF and low BMP activity across the entire skin reveals a latent dermal capacity to undergo spatially patterned self-organisation in the absence of epithelial direction. This mesenchymal self-organisation relies on restricted transforming growth factor (TGF) β signalling, which serves to drive chemotactic mesenchymal patterning when reaction–diffusion patterning is suppressed, but, in normal conditions, facilitates cell movement to locally prepatterned sources of FGF. This work illustrates a hierarchy of periodic patterning modes operating in organogenesis. Repeating anatomical units, forming a pattern, are present in different parts of the body. This is particularly obvious in the skin, where the many hair follicles become regularly arranged and fixed in place in the embryo as a pattern of evenly spaced spots. The basis for the formation of such repeating patterns has attracted a number of theoretical explanations. One influential theory is that cells first issue chemical signals to one another to produce a map of the pattern, which they then follow to assemble a structure, like a hair follicle. Alternative theories instead suggest that cells cluster together directly, without reference to a pre-existing map, to drive pattern formation. In this study, we find that a set of chemical signals known to be important for early hair follicle formation form a network capable of producing a patterned template to which cells then respond, moving according to its instructions. This supports the signal-based theory for pattern formation. Strikingly, though, by imposing the conditions of the incipient hair follicle evenly across the entire skin, we reveal that skin cells can also form patterns directly by coalescing, without requiring instructions from a pre-existing pattern. However, this ability of cells to pattern directly is normally subservient to their following of a quickly forming pattern template defined by chemical signals. This work highlights that different ways of making biological patterns can coexist in the same embryonic organ but that one is normally subordinated to the other.
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影响因子：
30.8
作者：
Economou, Andrew D.;Ohazama, Atsushi;Porntaveetus, Thantrira;Sharpe, Paul T.;Kondo, Shigeru;Basson, M. Albert;Gritli-Linde, Amel;Cobourne, Martyn T.;Green, Jeremy B. A.
通讯作者：
Green, Jeremy B. A.
DOI：
10.1126/science.1176009
发表时间：
2009-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hynes RO
通讯作者：
Hynes RO
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
11.4
作者：
HARDY, MH
通讯作者：
HARDY, MH
影响因子：
2.6
作者：
Grotewold, L;Plum, M;Rüther, U
通讯作者：
Rüther, U