Uncoupling sonic hedgehog control of pattern and expansion of the developing limb bud
Uncoupling sonic hedgehog control of pattern and expansion of the developing limb bud
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DOI：
10.1016/j.devcel.2008.01.008
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发表时间：
2008-04-01
影响因子：
11.8
通讯作者：
Mackem, Susan
中科院分区：
文献类型：
--
作者：
Zhu, Jianjian;Nakamura, Eiichiro;Mackem, Susan
在许多情况下调节增殖的Sonic hedgehog（Shh）作为肢体形态原来指定不同的手指模式。Shh对细胞数量的影响如何与其在指定数字身份中的作用有关尚不清楚。删除小鼠Shh基因在不同的时间使用条件Cre线，我们发现，Shh功能控制肢体发育在两个阶段：一个非常短暂的，早期的图案化阶段调节数字身份，和一个扩展的生长促进阶段，在此期间，数字前体间充质扩大，并成为招募到冷凝数字原基。我们的分析揭示了一个意想不到的正常哺乳动物手指形成交替前后顺序。在连续较早的Shh去除后，手指的逐渐丢失反映了这种交替序列，并突出了Shh在细胞扩增中的作用，以产生正常的手指互补。
Sonic hedgehog (Shh), which regulates proliferation in many contexts, functions as a limb morphogen to specify a distinct pattern of digits. How Shh's effects on cell number relate to its role in specifying digit identity is unclear. Deleting the mouse Shh gene at different times using a conditional Cre line, we find that Shh functions to control limb development in two phases: a very transient, early patterning phase regulating digit identity, and an extended growth-promoting phase during which the digit precursor mesenchyme expands and becomes recruited into condensing digit primordia. Our analysis reveals an unexpected alternating anterior-posterior sequence of normal mammalian digit formation. The progressive loss of digits upon successively earlier Shh removal mirrors this alternating sequence and highlights Shh's role in cell expansion to produce the normal digit complement.