The vertebrate nervous system is induced from the ectoderm by BMP inhibitors secreted from the Spemann organizer at gastrula stage. After neural induction, the vertebrate central nervous system (CNS) is patterned along the anterior-posterior and dorsal-ventral axis by an interplay of several signaling pathways that cross-talk to provide positional information and induce cell fate specification. Wnt, FGFs and retinoic acid signaling pathways are involved in anterior-posterior patterning and BMP and hedgehog signaling in dorsoventral patterning of the CNS. Wnt signaling was also shown to be important in dorsal neural fate specification. Downstream of these signaling molecules are a group of transcription factors that are specifically expressed in different regions which gradually assign different fates to the neural cells. However, the detailed regulatory network governing neural patterning is far from clear and the mechanisms of the fine tuning of the signaling during these processes are not well studied. The objective of our group is to understand the molecular mechanism of vertebrate neural patterning and its evolution during vertebrate origin. We use the Xenopus，mouse and the cephalochordate amphioxus as our model animals.
Recent work from our laboratory includes:
1, Using the amphibian Xenopus as model system, the lab has systematically studied the expression and functions of the genes involved in neural development, including Nkx6, Dbx2，Islet1，Brunol, RCOR2, ZMYND8, etc.
2, Neural crest is a multipotent cell population which originates at the border between the neural plate and epidermis and is a vertebrate innovation during evolution. We identified Nkx6.3 as a key regulator of neural crest development and border formation through the modulation of Wnt signaling. We found that the reduced folic acid carrier (RFC) mediated folate metabolic pathway potentiates neural crest gene expression through epigenetic modifications.
3, The patterning of the midbrain and hindbrain is governed by a signaling center at the mid-hindbrain boundary (MHB). We found that Nkx6.1 and Nkx6.2 are required for MHB formation in Xenopus embryos, likely by modulating Wnt1 expression. We also identified RNF220 as a new player in mid-hindbrain development in both Xenopus and mouse. RNF220 encodes an ubiquitin E3 ligase and is specifically expressed in ventral part of the spinal cord and mid-hindbrain. The RNF220 knockout mice showed severe defects in midbrain and hindbrain development. Mechanismly, we found that RNF220 likely works through promoting Wnt signaling via USP7 mediated deubiquitination of beta-catenin.
4, The cephalochordate amphioxus, a representative of the primitive chordate, shares the same basic body plan as vertebrates and is an important model to understand the origin of vertebrate body plan. We are carrying out a transcriptome analysis and developmental gene expression profiling of amphioxus embryos, aiming to establish a platform to understand the mechanisms of neural patterning in this animal.