Department of Biochemistry and Molecular Biology, University of Texas, MD Anderson Cancer Center, Houston, Texas 77030, USA.
Dev Dyn. 2010 Aug;239(8):2161-71. doi: 10.1002/dvdy.22347.
Studies of Lmx1b have shown that it is required for anterior segment formation during embryonic development and that reduction of Lmx1b may contribute to elevated intraocular pressure in the adult. However, whether Lmx1b is required for formation of anterior segment tissues that are associated with regulation of intraocular pressure has not been addressed due to the perinatal lethality of Lmx1b null allele. Here we use conditional deletion strategies to circumvent perinatal lethality. Our results indicate that Lmx1b is required in neural crest-derived periocular mesenchyme for formation of anterior segment tissues, including trabecular meshwork, a critical regulator of intraocular pressure. Furthermore, we show that Lmx1b is essential to maintain proper functioning of those tissues in the adult. Taken together, our results are the first to link a specific transcription factor to trabecular meshwork formation and the first to demonstrate specific requirements for Lmx1b in maintaining the integrity of adult anterior segment.
研究 Lmx1b 表明,它在胚胎发育过程中对于前节的形成是必需的,并且 Lmx1b 的减少可能导致成年人眼内压升高。然而,由于 Lmx1b 缺失等位基因具有围产期致死性,因此尚未确定 Lmx1b 是否需要形成与调节眼内压相关的前节组织。在这里,我们使用条件性缺失策略来规避围产期致死性。我们的结果表明,Lmx1b 在神经嵴衍生的眶周间质中对于前节组织的形成是必需的,包括小梁网,这是眼内压的关键调节因子。此外,我们表明,Lmx1b 对于维持这些组织在成年期的正常功能是必不可少的。总之,我们的结果首次将特定的转录因子与小梁网形成联系起来,并首次证明了 Lmx1b 在维持成人前节完整性方面的具体要求。