Harata Ayano, Hirakawa Mika, Sakuma Tetsushi, Yamamoto Takashi, Hashimoto Chikara
JT Biohistory Research Hall, Takatsuki, Japan.
Department of Mathematical and Life Sciences, Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Japan.
Dev Growth Differ. 2019 Feb;61(2):186-197. doi: 10.1111/dgd.12563. Epub 2018 Aug 1.
Vertebrates have unique head structures that are mainly composed of the central nervous system, the neural crest, and placode cells. These head structures are brought about initially by the neural induction between the organizer and the prospective neuroectoderm at early gastrula stage. Purinergic receptors are activated by nucleotides released from cells and influence intracellular signaling pathways, such as phospholipase C and adenylate cyclase signaling pathways. As P2Y receptor is vertebrate-specific and involved in head formation, we expect that its emergence may be related to the acquisition of vertebrate head during evolution. Here, we focused on the role of p2ry4 in early development in Xenopus laevis and found that p2ry4 was required for the establishment of the head organizer during neural induction and contributed to head formation. We showed that p2ry4 was expressed in the head organizer region and the prospective neuroectoderm at early gastrula stage, and was enriched in the head components. Disruption of p2ry4 function resulted in the small head phenotype and the reduced expression of marker genes specific for neuroectoderm and neural border at an early neurula stage. Furthermore, we examined the effect of p2ry4 disruption on the establishment of the head organizer and found that a reduction in the expression of head organizer genes, such as dkk1 and cerberus, and p2ry4 could also induce the ectopic expression of these marker genes. These results suggested that p2ry4 plays a key role in head organizer formation. Our study demonstrated a novel role of p2ry4 in early head development.
脊椎动物具有独特的头部结构，主要由中枢神经系统、神经嵴和基板细胞组成。这些头部结构最初是在原肠胚早期由组织者与预期的神经外胚层之间的神经诱导产生的。嘌呤能受体被细胞释放的核苷酸激活，并影响细胞内信号通路，如磷脂酶C和腺苷酸环化酶信号通路。由于P2Y受体是脊椎动物特有的且参与头部形成，我们推测其出现可能与脊椎动物头部在进化过程中的获得有关。在此，我们聚焦于p2ry4在非洲爪蟾早期发育中的作用，发现p2ry4在神经诱导过程中对于头部组织者的建立是必需的，并且有助于头部形成。我们发现p2ry4在原肠胚早期在头部组织者区域和预期的神经外胚层中表达，并在头部成分中富集。p2ry4功能的破坏导致小头表型以及在神经胚早期神经外胚层和神经边界特异性标记基因的表达减少。此外，我们研究了p2ry4破坏对头部组织者建立的影响，发现头部组织者基因如dkk1和cerberus的表达减少，并且p2ry4也能诱导这些标记基因的异位表达。这些结果表明p2ry4在头部组织者形成中起关键作用。我们的研究证明了p2ry4在早期头部发育中的新作用。
