Cabrera Pereira Angel, Dasgupta Krishnakali, Ho Thach-Vu, Pacheco-Vergara Maria, Kim Julie, Kataria Niam, Liang Yaowei, Mei Jeslyn, Yu Jinyeong, Witek Lukasz, Chai Yang, Jeong Juhee
Department of Molecular Pathobiology, College of Dentistry, New York University, New York, NY, United States.
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, United States.
Front Physiol. 2023 Aug 1;14:1225118. doi: 10.3389/fphys.2023.1225118. eCollection 2023.
The calvaria (top part of the skull) is made of pieces of bone as well as multiple soft tissue joints called sutures. The latter is crucial to the growth and morphogenesis of the skull, and thus a loss of calvarial sutures can lead to severe congenital defects in humans. During embryogenesis, the calvaria develops from the cranial mesenchyme covering the brain, which contains cells originating from the neural crest and the mesoderm. While the mechanism that patterns the cranial mesenchyme into bone and sutures is not well understood, function of , a gene encoding a LIM-domain homeodomain transcription factor, plays a key role in this process. In the current study, we investigated a difference in the function of in different parts of the calvaria using neural crest-specific and mesoderm-specific mutants. We found that was obligatory for development of the interfrontal suture and the anterior fontanel along the dorsal midline of the skull, but not for the posterior fontanel over the midbrain. Also, mutation in the neural crest-derived mesenchyme, but not the mesoderm-derived mesenchyme, had a non-cell autonomous effect on coronal suture development. Furthermore, overexpression of in the neural crest lineage had different effects on the position of the coronal suture on the apical part and the basal part. Other unexpected phenotypes of mutants led to an additional finding that the coronal suture and the sagittal suture are of dual embryonic origin. Together, our data reveal a remarkable level of regional specificity in regulation of calvarial development.
颅盖骨（颅骨顶部）由多块骨头以及多个称为缝线的软组织关节组成。后者对颅骨的生长和形态发生至关重要，因此颅盖骨缝线的缺失会导致人类严重的先天性缺陷。在胚胎发育过程中，颅盖骨由覆盖大脑的颅间充质发育而来，颅间充质包含源自神经嵴和中胚层的细胞。虽然将颅间充质分化为骨头和缝线的机制尚不清楚，但Lhx2（一种编码LIM结构域同源结构域转录因子的基因）的功能在这一过程中起关键作用。在本研究中，我们使用神经嵴特异性和中胚层特异性Lhx2突变体研究了Lhx2在颅盖骨不同部位功能的差异。我们发现，Lhx2对于沿颅骨背中线的额间缝和前囟门的发育是必需的，但对中脑上方的后囟门发育不是必需的。此外，神经嵴衍生的间充质中的Lhx2突变，而非中胚层衍生的间充质中的Lhx2突变，对冠状缝发育具有非细胞自主性效应。此外，在神经嵴谱系中过表达Lhx2对冠状缝在顶部和基部的位置有不同影响。Lhx2突变体的其他意外表型导致了另一个发现，即冠状缝和矢状缝具有双重胚胎起源。总之，我们的数据揭示了颅盖骨发育调控中显著的区域特异性水平。
