Sculpting skin appendages out of epidermal layers via temporally and spatially regulated apoptotic events

Sculpting skin appendages out of epidermal layers via temporally and spatially regulated apoptotic events
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DOI:
10.1111/j.0022-202x.2004.22611.x
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发表时间:
2004-06-01
影响因子:
6.5
通讯作者:
Chuong, CM
Chuong, CM
中科院分区:
医学1区
文献类型:
--
作者:
Chang, CH;Yu, MK;Chuong, CM

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复杂的皮肤附属物是由表皮细胞通过各种细胞事件建立的。在这里,我们使用TUNEL和caspase-3免疫定位检测羽毛形态发生中的细胞凋亡。我们推导出三种模式。在模式1A中,细胞凋亡发生在局部生长区(LoGZ)内以调节生长(羽芽)。在模式1B中,形态原分泌细胞存在于LoGZ附近,并且细胞凋亡可能起作用以去除这样的信号传导中心(倒钩脊)。在模式2中,角质形成细胞在终末分化前分化,并在分支之间留下空间(边缘板)。在模式3A中,角质形成细胞角质化并剥落以游离皮肤附属物(羽鞘、牙髓上皮)。在模式3B中,角化的表皮细胞变成永久性结构(轴、支、小突起)。因此,不同的凋亡模式对形态发生具有不同的影响。我们进一步测试了不平衡的Shh对细胞凋亡的影响。Shh抑制可减少边缘板的凋亡,并引起微管板的异常分化。Shh过表达增强倒刺嵴的增殖。Patched在小臂板上皮中的表达暗示了旁分泌机制。目前的工作补充了我们最近在LoGZ上的工作,以显示如何以时间和空间特定的方式添加和移除细胞团,以协调从表皮层雕刻皮肤附属物。
Complex skin appendages are built from the epidermal cells through various cell events. Here we used TUNEL and caspase-3 immuno-localization to examine apoptosis in feather morphogenesis. We deduced three modes. In Mode 1A, apoptosis occurs within the localized growth zone (LoGZ) to regulate growth (feather buds). In Mode 1B, morphogen secreting cells are present adjacent to LoGZ and apoptosis may work to remove such signaling centers (barb ridges). In Mode 2, keratinocytes apoptosed before terminal differentiation and left spaces between branches (marginal plate). In Mode 3A, keratinocytes cornified and flaked off to free skin appendages (feather sheath, pulp epithelium). In Mode 3B, keratinized apoptosed epithelial cells became permanent structures (rachis, ramus, barbules). Thus, different apoptotic modes can have different impacts on morphogenesis. We further tested effects of imbalanced Shh on apoptosis. Shh suppression reduced marginal plate apoptosis and caused abnormal differentiation of barbule plates. Shh over-expression enhanced proliferation in barb ridges. Expression of Patched in the barbule plate epithelia implies a paracrine mechanism. The current work complements our recent work on LoGZ to show how adding and removing cell masses in temporally and spatially specific ways are coordinated to sculpt skin appendages from epidermal layers.