Saint-Germain Natasha, Lee Young-Hoon, Zhang Yanhui, Sargent Thomas D, Saint-Jeannet Jean-Pierre
Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
Development. 2004 Apr;131(8):1755-63. doi: 10.1242/dev.01066. Epub 2004 Mar 17.
The vertebrate inner ear develops from a thickening of the embryonic ectoderm, adjacent to the hindbrain, known as the otic placode. All components of the inner ear derive from the embryonic otic placode. Sox proteins form a large class of transcriptional regulators implicated in the control of a variety of developmental processes. One member of this family, Sox9, is expressed in the developing inner ear, but little is known about the early function of Sox9 in this tissue. We report the functional analysis of Sox9 during development of Xenopus inner ear. Sox9 otic expression is initiated shortly after gastrulation in the sensory layer of the ectoderm, in a bilateral patch of cells immediately adjacent to the cranial neural crest. In the otic placode, Sox9 colocalizes with Pax8 one of the earliest gene expressed in response to otic placode inducing signals. Depletion of Sox9 protein in whole embryos using morpholino antisense oligonucleotides causes a dramatic loss of the early otic placode markers Pax8 and Tbx2. Later in embryogenesis, Sox9 morpholino-injected embryos lack a morphologically recognizable otic vesicle and fail to express late otic markers (Tbx2, Bmp4, Otx2 and Wnt3a) that normally exhibit regionalized expression pattern throughout the otocyst. Using a hormone inducible inhibitory mutant of Sox9, we demonstrate that Sox9 function is required for otic placode specification but not for its subsequent patterning. We propose that Sox9 is one of the key regulators of inner ear specification in Xenopus.
脊椎动物的内耳由胚胎外胚层增厚形成，该外胚层增厚部分紧邻后脑，被称为耳基板。内耳的所有组成部分均源自胚胎耳基板。Sox蛋白构成了一大类转录调节因子，参与多种发育过程的调控。该家族的一个成员Sox9在发育中的内耳中表达，但关于Sox9在此组织中的早期功能却知之甚少。我们报告了非洲爪蟾内耳发育过程中Sox9的功能分析。Sox9在原肠胚形成后不久，在外胚层的感觉层中开始表达，位于紧邻颅神经嵴的双侧细胞区域。在耳基板中，Sox9与Pax8共定位，Pax8是最早响应耳基板诱导信号而表达的基因之一。使用吗啉代反义寡核苷酸在全胚胎中耗尽Sox9蛋白，会导致早期耳基板标记物Pax8和Tbx2显著缺失。在胚胎发育后期，注射Sox9吗啉代的胚胎缺乏形态上可识别的耳泡，并且无法表达后期耳标记物（Tbx2、Bmp4、Otx2和Wnt3a），这些标记物通常在整个耳囊中呈现区域化表达模式。使用Sox9的激素诱导抑制突变体，我们证明Sox9的功能对于耳基板的特化是必需的，但对于其后续的模式形成并非必需。我们提出Sox9是非洲爪蟾内耳特化的关键调节因子之一。
