@article{Development:3674,
      recid = {3674},
      author = {Meng, Julia L},
      title = {Development of Motor Circuits: From Neuronal Stem Cells  and Neuronal Diversity to Motor Circuit Assembly},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2022-03},
      pages = {320},
      abstract = {How circuits assemble starting from stem cells is a  fundamental question in developmental neurobiology. Dynamic  gene expression in stem cells contribute to molecular  diversity of neuronal progeny. Morphology and synaptic  connections of neurons are important for circuit  organization and function. However, less clear is the  relationship between molecular diversity and the  specification of neuronal morphology and synaptic  partnerships. Here, I tested the hypothesis that dynamic  gene expression in neural stem cells is a general strategy  underlying neuronal integration into circuits. To do so, I  used the Drosophila larval motor system. This system offers  unparalleled resolution of neural stem cells as well as  neurons at single-cell and -synapse resolution. The  Heckscher lab discovered that neuronal birth time and  circuit membership are correlated (Wreden et al., 2017).  This finding implies that time-linked information plays an  instructive role for circuit membership. At the time of  birth, neurons receive information from two sources:  intrinsic –inherited from their stem cell parent and  extrinsic –cues from their environment. As development  progresses, intrinsic and extrinsic cues change  simultaneously. To uncouple intrinsic cues from  developmental time in stem cells, I specifically  manipulated dynamically-expressed transcription factors  called temporal factors. Temporal factors act in Drosophila  stem cells (neuroblasts), to specify embryonic molecular  marker expression in neuronal progeny.  Using genetic  approaches, I altered the temporal dynamics of  transcription factor expression in a neuroblast  lineage-specific manner. Then, I performed neuromuscular  dissections, single-cell tracing, labeling with marker  genes, confocal imaging, electrophysiology (in  collaboration), and calcium imaging to examine motor neuron  morphology and synaptic connectivity (Meng et al., 2019;  2020). I found that temporal transcription factors acting  in neuroblast are potent regulators of functional motor  neuron-to-muscle synaptic partnerships, but that the local  local synaptic environment can also influence synaptic  partnerships. Further, my data revealed that molecular  markers used to assess embryonic neuronal fate do not  faithfully correlate with motor neuron to muscle synaptic  partnerships. Altogether, my data demonstrates that  intrinsic information strongly influences circuit assembly  decisions. Next, since the environment greatly differs in  the bodywall muscle periphery vs the CNS I characterized  the dendrite morphology of single motor neurons and  interneurons within the larval CNS. Here, I found evidence  that intrinsic information strongly influences motor neuron  dendrite morphology (Meng et al., 2019), but may have less  of an impact on interneuron dendrite morphologies  (unpublished, work in progress). This suggests, there are  likely differences in strategies underlying synaptic  partnership decisions in the periphery versus the CNS. To  understand these differences, future research will need to  obtain single-synapse resolution of synaptic partnerships  formed within the CNS. To further elucidate intrinsic  molecular programs specifying motor neuron to muscle  synaptic partnership decisions, I manipulated other  intrinsic, early acting factors (e.g. Notch, Hb9, and Eve).  These unpublished experiments further support the  hypothesis that inherited information from neural stem cell  parents is likely a general strategy underlying neuronal  integration into circuits. More broadly, strategies  underlying motor circuit assembly identified in the  Drosophila larval system are likely repeated throughout the  Animal Kingdom where motor circuits are essential for  locomotion.  },
      url = {http://knowledge.uchicago.edu/record/3674},
      doi = {https://doi.org/10.6082/uchicago.3674},
}