Chen H, Ovchinnikov D, Pressman C L, Aulehla A, Lun Y, Johnson R L
Department of Biochemistry and Molecular Biology, UT MD Anderson Cancer Center, Houston 77030, USA.
Dev Genet. 1998;22(4):314-20. doi: 10.1002/(SICI)1520-6408(1998)22:4<314::AID-DVG2>3.0.CO;2-9.
The vertebrate cranial vault, or calvaria, forms during embryonic development from cranial mesenchyme of multiple embryonic origins. Inductive interactions are thought to specify the number and location of the calvarial bones, including interactions between the neuroepithelium and cranial mesenchyme. An important feature of calvarial development is the local inhibition of osteogenic potential which occurs between specific bones and results in the formation of the cranial sutures. These sutures allow for postnatal growth of the skull to accommodate postnatal increase in brain size. The molecular genetic mechanisms responsible for the patterning of individual calvarial bones and for the specification of the number and location of sutures are poorly understood at the molecular genetic level. Here we report on the function and expression pattern of the LIM-homeodomain gene, lmx1b, during calvarial development. Lmx1b is expressed in the neuroepithelium underlying portions of the developing skull and in cranial mesenchyme which contributes to portions of the cranial vault. Lmx1b is essential for proper patterning and morphogenesis of the calvaria since the supraoccipital and interparietal bones of lmx1b mutant mice are either missing or severely reduced. Moreover, lmx1b mutant mice have severely abnormal sutures between the frontal, parietal, and interparietal bones. Our results indicate that lmx1b is required for multiple events in calvarial development and suggest possible genetic interaction with other genes known to regulate skull development and suture formation.
脊椎动物的颅顶，即头盖骨，在胚胎发育过程中由多种胚胎起源的颅间充质形成。诱导性相互作用被认为决定了头盖骨的数量和位置，包括神经上皮与颅间充质之间的相互作用。头盖骨发育的一个重要特征是特定骨骼之间发生的成骨潜能的局部抑制，这导致了颅缝的形成。这些颅缝允许出生后颅骨生长，以适应出生后大脑大小的增加。在分子遗传学水平上，负责单个头盖骨形成以及颅缝数量和位置确定的分子遗传机制仍知之甚少。在此，我们报告了LIM同源结构域基因lmx1b在头盖骨发育过程中的功能和表达模式。Lmx1b在发育中颅骨部分下方的神经上皮以及对头盖骨部分有贡献的颅间充质中表达。Lmx1b对头盖骨的正确形成和形态发生至关重要，因为lmx1b突变小鼠的枕上骨和顶间骨要么缺失，要么严重减少。此外，lmx1b突变小鼠在额骨、顶骨和顶间骨之间有严重异常的颅缝。我们的结果表明，lmx1b是头盖骨发育中多个事件所必需的，并提示其可能与其他已知调节颅骨发育和颅缝形成的基因存在遗传相互作用。
