000004811 001__ 4811
000004811 005__ 20251007025210.0
000004811 0247_ $$2doi$$a10.6082/uchicago.4811
000004811 037__ $$aTHESIS$$bDissertation
000004811 041__ $$aeng
000004811 245__ $$aThe Non-canonical Role of Hox Genes in the Regulation and Maintenance of C. elegans Motor Neuron Terminal Identity
000004811 260__ $$bUniversity of Chicago
000004811 269__ $$a2022-08
000004811 300__ $$a250
000004811 336__ $$aDissertation
000004811 502__ $$bPh.D.
000004811 520__ $$aHox transcription factors play fundamental roles during early patterning, but they are also expressed continuously, from embryonic stages through adulthood, in the nervous system. However, the functional significance of their sustained expression remains unclear. In C. elegans motor neurons, we identified a non-canonical role of Hox genes in the regulation and maintenance of ventral nerve cord motor neuron terminal identity. First, we are among the first groups to establish the MN expression profile of Hox genes with single cell resolution. Second, we demonstrated the functions of Hox proteins in regulating neurotransmitter pathway genes and a broad range of motor neuron terminal identity genes. LIN-39 (Scr/Dfd/Hox4-5) is continuously required during post-embryonic life to maintain neurotransmitter identity, a core element of neuronal function. LIN-39 acts directly to co-regulate genes that define cholinergic identity (e.g., unc-17/VAChT, cho-1/ChT). We further show that LIN-39, MAB-5 (Antp/Hox6-8) and the transcription factor UNC-3 (Collier/Ebf) operate in a positive feedforward loop to ensure continuous and robust expression of cholinergic identity genes. Third, we identified a two- component design principle for homeostatic control of Hox gene expression in adult MNs (Hox transcriptional autoregulation is counterbalanced by negative UNC-3 feedback). Last, we described a Hox transcriptional switch prevented by UNC-3 to safeguard cholinergic motor neuron identity throughout life. These findings not only highlighted the noncanonical role but also established a terminal selector role for Hox proteins during post-embryonic life, critically broadening their functional repertoire from early patterning to the control of motor neuron terminal identity.
000004811 540__ $$a© 2022 Weidong Feng
000004811 650__ $$aDevelopmental biology
000004811 650__ $$aNeurosciences
000004811 650__ $$aGenetics
000004811 653__ $$aC. elegans
000004811 653__ $$aHox gene
000004811 653__ $$amotor neuron
000004811 653__ $$aterminal identity
000004811 690__ $$aBiological Sciences Division
000004811 690__ $$aPritzker School of Medicine
000004811 691__ $$aDevelopment, Regeneration, and Stem Cell Biology
000004811 7001_ $$aFeng, Weidong$$uUniversity of Chicago
000004811 72012 $$aPaschalis Kratsios
000004811 72012 $$aEdwin Ferguson
000004811 72014 $$aPaschalis Kratisos
000004811 72014 $$aEdwin Ferguson
000004811 72014 $$aElizabeth Heckscher
000004811 72014 $$aMarcelo Nobrega
000004811 8564_ $$9003fbaef-7664-4d65-88ab-e8562da5acdd$$s11900335$$uhttps://knowledge.uchicago.edu/record/4811/files/Feng_uchicago_0330D_16496.pdf$$ePublic
000004811 909CO $$ooai:uchicago.tind.io:4811$$pDissertations$$pGLOBAL_SET
000004811 983__ $$aDissertation