Bin Yu, Xiaolin Wang, Shuai Wei, Tao Fu, Emmanuel Enoch Dzakah, Ahmed Waqas, Walter W. Walthall, Ge Shan. Convergent transcriptional programs regulate cAMP levels in C. elegans GABAergic motor neurons. Dev. Cell. 2017, Online.
Both transcriptional regulation and signaling pathways play crucial roles in neuronal differentiation and plasticity. Caenorhabditis elegans possesses 19 GABAergic motor neurons (MNs) called D MNs, which are divided into two subgroups as DD and VD. DD but not VD MNs reverse their cellular polarity in a developmental process called respecification. UNC-30 and UNC-55 are two critical transcription factors in D MNs. By chromatin immunoprecipitation with CRISPR/cas9 knock-in of GFP fusion, we uncovered the global targets of UNC-30 and UNC-55. UNC-30 and UNC-55 are largely converged to regulate over 1,300 noncoding and coding genes, and genes in multiple biological processes including the cAMP metabolism are co-regulated. Increase of cAMP levels may serve as a timing signal for respecification, whereas UNC-55 regulates genes such as pde-4 to keep the cAMP levels low in VD. Other genes modulating DD respecification such as lin-14, irx-1, and oig-1 are also found to affect cAMP levels.