The missions of the Center for Developmental Biology (CDB) are focusing on fundamental questions of development of both plants and animals using model organisms such as C. elegans, Drosophila, Xenopus, zebrafish, mouse, monkey, Arabidopsis and rice, and to develop innovative technology to meet our national needs in agriculture and human health. Currently CDB has 24 research groups. There are 12 principal investigators (PI) who were awarded the National Science Fund for Distinguished Young Scholars, During 2016, the Center for Developmental Biology has made substantial progress in the following fields.
Early Development: Weicai Yang’s group reported the identification of a cell-surface receptor heteromer, MDIS1-MIK, on the pollen tube that perceives the female attractant LURE1 in Arabidopsis thaliana. This finding identified the long-puzzled receptor heteromer of the LURE1 attractant and revealed the activation mechanism and will contribute to the full understanding of male-female recognition during plant reproduction. Meanwhile, this study establishes the theory of through inter-species expressing of receptor to break down the reproductive isolation and will shed light on the crop breeding (Wang et al., Nature, 2016). In the Solanaceae, Rosaceae and Plantaginaceae, the S-locus encodes a single S-RNase and a cluster of S-locus F-box (SLF) proteins to control the pistil and pollen expression of SI, respectively. Yongbiao Xue’s group revealed that the electrostaticpotentials act as a major physical force between cytosolic SLFs and S-RNases, providing a mechanistic insight into the self/non-self-discrimination between cytosolic proteins in angiosperms (Li et al., Plant J, 2016). Large numbers of maternal RNAs are deposited in oocytes and are reserved for later development. Jian Zhang’ group reported loss of Zar1 causes markedly upregulation of zona pellucida (ZP) family proteins, while overexpression of ZP proteins in oocytes causes upregulation of stress related activating transcription factor 3 (atf3), arguing that tightly controlled translation of ZP proteins is essential for ER homeostasis during early oogenesis. Furthermore, Zar1 binds to zona pellucida (zp) mRNAs and represses their translation (Miao et al., Development, 2016).
Neurodevelopment and Disease: Zhiheng Xu’s group and Guoli Ming’s group at Johns Hopkins University revealed that Crmp2 (collapsing response mediator protein 2), a schizophrenia risk gene, plays a critical role in neural development, circuit integrity and brain function. They provided a valuable mouse model for better understanding the aetiology of schizophrenia and targeted strategies for drug development (Zhang et al., Nat Commun, 2016). Xu’s group also demonstrated MEA6 plays a critical role in lipid transportation through the coordinated regulation of the COPII machinery, which provided insights into mechanisms underlying VLDL transportation. More importantly, this mouse model provides a useful tool for potential biomarkers or drug screening related to fatty liver disease (Wang et al., Cell Res, 2016).Mei Ding’s group found that the single calponin homology (CH) domain-containing protein CHDP-1 induces the formation of cell protrusions by couplingmembrane expansion to Rac1-mediated actin dynamicsin Caenorhabditis elegans (Guan et al., PLoS Genet, 2016). Xiaojiang Li’s group revealed age- and cell typedependent vital functions of Htt (huntingtin, Huntington’s disease protein) and the safety of knocking down neuronal Htt expression in adult brains as a treatment (Wang et al., PNAS, 2016; Liu et al., PLoS Genet, 2016). The study of Yongqing Zhang’s group study sheds new light onto the neuronal functions of UBE3A (E3 ubiquitin ligase) and provides novel perspectives for understanding the pathogenesis of UBE3A-associated Angelman syndrome and autism (Li et al., PLoS Genet, 2016).
Stem Cell and Tissue Engineering: Zhiheng Xu’s group gave direct evidence that Zika infection causes microcephaly in a mammalian animal model. They found the virus infected the neural progenitor cells, and infected brains reveal expression of genes related to viral entry, altered immune response, and cell death. Further study showed passive transfer of convalescent serum containing high-titer neutralizing antibodies to pregnant mice can not only suppress ZIKV replication but also inhibit cell death and reduction of neural progenitor cells in infected fetal brains, thus preventing microcephaly (Wang et al., Cell Res, 2016). Jianwu Dai’s group screened a functional scaffold, on which the cultured neural stem cells (NSCs) show high neuronal differentiation rate and generate both sensory and motor mature neurons. They transplanted the functional scaffold into a rat severe spinal cord injury model, which showed that higher endogenous neurogenesis efficiency as well as in vivo survival and neuronal differentiation rate of the grafted NSCs are observed (Li et al., Adv Funct Mater, 2016).
Lipid Metabolism and Development: John Speakman’s group used public domain data to locate signatures of positive selection based on derived allele frequency, genetic diversity, long haplotypes, and differences between populations at SNPs identified in genome-wide association studies (GWASs) for BMI. The widespread absence of signatures of positive selection, combined with selection favoring leanness at some alleles, does not support the suggestion that obesity provided a selective advantage to survive famines, or any other selective advantage (Wang et al., Cell Metab, 2016). Using state-of-the-art lipidomic approach, Guanghou Shui’s group found a breakdown in DHA esterification into neural membranes may prove more detrimental than a diminished dietary supply of DHA per se (Lam et al., Oncotarget, 2016).
Vesicle Trafficking and Development: Together with Xiaojiang Hao’s group at Kunming Institute of Botany, CAS, Chonglin Yang’s group showed that protein kinase C couples activation of the TFEB transcription factor with inactivation of the ZKSCAN3 transcriptional repressor through two parallel signaling cascades. It revealed that PKC activators are viable treatment options for lysosome-related disorders (Li et al., Nature Cell Biol, 2016). Phosphatidylinositol 3-phosphate (PtdIns3P) plays a central role in endosome fusion, recycling, sorting, and early-to-late endosome conversion. Yang’s group identified two new factors, SORF-1 and SORF-2, as essential PtdIns3P regulators in C. elegans. These findings revealed a conserved mechanism that controls appropriate PtdIns3P levels in early-to-late endosome conversion (Liu et al., J Cell Biol, 2016).
