@article{Non-canonical:4811,
      recid = {4811},
      author = {Feng, Weidong},
      title = {The Non-canonical Role of Hox Genes in the Regulation and  Maintenance of C. elegans Motor Neuron Terminal Identity},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2022-08},
      pages = {250},
      abstract = {Hox 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.},
      url = {http://knowledge.uchicago.edu/record/4811},
      doi = {https://doi.org/10.6082/uchicago.4811},
}