Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse.
Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse.
复制标题
胚胎视黄酸合成是小鼠前肢生长和前后图案形成所必需的。
作者：
K. Niederreither;J. Vermot;B. Schuhbaur;P. Chambon;P. Dollé
许多研究，经常进行的鸟类胚胎，有牵连的视黄酸（RA）在控制肢芽的生长和图案。在这里，我们已经调查是否缺乏内源性RA合成影响肢体形态发生在突变小鼠胚胎缺乏的视黄醇脱氢酶2（Raldh 2/Aldh 1a 2）。这些突变体，除了在发育中的视网膜中没有可检测到的胚胎RA，在E9.5-E10死亡，没有任何肢芽形成的证据，但是从E7.5开始通过口服管饲法补充母体RA可以延长它们的存活。这些幸存者表现出高度退化的前肢雏形，但显然是正常的后肢。通过在母体食物中提供RA，我们发现了拯救前肢生长和模式的阶段和剂量依赖性。在从E7.5至8.5补充RA后，突变前肢明显发育不全，缺乏前后（AP）模式，具有单个内侧软骨和1-2个手指雏形。在E9.5之前提供RA显著挽救前肢生长，但不能恢复正常的AP模式。增加RA剂量可以挽救缺指畸形，但会导致手指模式不对称，第一手指异常长或对称性多指畸形。突变前肢芽的特点是缺乏表达或异常的远端分布的Sonic hedgehog（Shh）转录本，有时具有最高的表达前部。还观察到Fgf 4的下调或异位前表达。结果，基因如Bmp 2或Hoxd基因沿着前肢芽的AP轴对称地表达，和/或稍后，在直足动物中。我们认为，RA信号合作与一个后限制因素，如dHand，产生一个功能区的极化活动（ZPA）。
Numerous studies, often performed on avian embryos, have implicated retinoic acid (RA) in the control of limb bud growth and patterning. Here we have investigated whether the lack of endogenous RA synthesis affects limb morphogenesis in mutant mouse embryos deficient for the retinaldehyde dehydrogenase 2 (Raldh2/Aldh1a2). These mutants, which have no detectable embryonic RA except in the developing retina, die at E9.5-E10 without any evidence of limb bud formation, but maternal RA supplementation through oral gavage from E7.5 can extend their survival. Such survivors exhibit highly reduced forelimb rudiments, but apparently normal hindlimbs. By providing RA within maternal food, we found both a stage- and dose-dependency for rescue of forelimb growth and patterning. Following RA supplementation from E7.5 to 8.5, mutant forelimbs are markedly hypoplastic and lack anteroposterior (AP) patterning, with a single medial cartilage and 1-2 digit rudiments. RA provided until E9.5 significantly rescues forelimb growth, but cannot restore normal AP patterning. Increasing the RA dose rescues the hypodactyly, but leads to lack of asymmetry of the digit pattern, with abnormally long first digit or symmetrical polydactyly. Mutant forelimb buds are characterized by lack of expression or abnormal distal distribution of Sonic hedgehog (Shh) transcripts, sometimes with highest expression anteriorly. Downregulation or ectopic anterior expression of Fgf4 is also seen. As a result, genes such as Bmp2 or Hoxd genes are expressed symmetrically along the AP axis of the forelimb buds, and/or later, of the autopod. We suggest that RA signaling cooperates with a posteriorly restricted factor such as dHand, to generate a functional zone of polarizing activity (ZPA).
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影响因子：
4.6
作者：
G. Drossopoulou;K. Lewis;J. Sanz-Ezquerro;N. Nikbakht;A. McMahon;C. Hofmann;C. Tickle
通讯作者：
G. Drossopoulou;K. Lewis;J. Sanz-Ezquerro;N. Nikbakht;A. McMahon;C. Hofmann;C. Tickle
有证据表明 Shh 与视黄酸诱导辅助因子合作建立 ZPA 样活性。
DOI：
10.1242/dev.122.2.537
发表时间：
1996
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Ogura,T;Alvarez,IS;Vogel,A;Rodríguez,C;Evans,RM;IzpisúaBelmonte,JC
通讯作者：
IzpisúaBelmonte,JC
β-apo-10-类胡萝卜素支持维生素 A 缺乏期间的正常胚胎发育。
影响因子：
4.6
作者：
Spiegler,Elizabeth;Kim,Youn-Kyung;Hoyos,Beatrice;Narayanasamy,Sureshbabu;Jiang,Hongfeng;Savio,Nicole;CurleyJr,RobertW;Harrison,EarlH;Hammerling,Ulrich;Quadro,Loredana
通讯作者：
Quadro,Loredana
影响因子：
10.5
作者：
Robin A. Kimmel;D. Turnbull;V. Blanquet;W. Wurst;C. Loomis;A. Joyner
通讯作者：
Robin A. Kimmel;D. Turnbull;V. Blanquet;W. Wurst;C. Loomis;A. Joyner
ZPA 的建立和 ZPA 形成介质 Hoxb-8 的表达需要类视黄醇信号传导。
DOI：
10.1242/dev.124.9.1643
发表时间：
1997
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Lu,HC;Revelli,JP;Goering,L;Thaller,C;Eichele,G
通讯作者：
Eichele,G