18 research outputs found
Coordinating differentiation with behavioral output of the CCAP-neuron network in Drosophila melanogaster.
Appropriate integration of neurons into functioning networks is the ultimate goal of
neuronal differentiation. My thesis examined the mechanism and timing of neuronal
differentiation in Drosophila melanogaster in relation to the functional requirements of a
developing neuronal network.
Specifically, my thesis aimed to address the role of extrinsic signaling in inducing and
maintaining the expression of genes important to the function of neurons within their network.
CCAP-neurons were chosen as a model because: 1) GAL4 drivers are available for cell-specific
genetic manipulation. 2) The critical role of CCAP-neurons in the behavior, ecdysis, provides for
an easily assayed phenotype if these neurons fail to function properly. 3) Four peptide hormones
are selectively expressed in differentiated CCAP-neurons that are essential for the normal
function of CCAP-neurons in ecdysis; this provides a direct link between gene expression and
behavior. 4) Ecdysis is reiterated at multiple developmental steps, thus the CCAP-neuronal
population functions throughout development. Together, these factors allow my work to relate
neuronal subtype-specific differentiation to the regulation of gene expression and then directly to
behavior.
Larval Drosophila CCAP-neurons comprise ~46 neurons [~36 interneurons (CCAP-INs)
and 10 efferent-neurons (CCAP-ENs)] that express a number of terminal differentiation genes
(TDGs; such as neuropeptides). To begin, we delineated mechanisms underlying the expression
of four TDGs, the peptide hormones CCAP, MIP, Bursicon-α and Bursicon-β, which together
mediate the functional output of those neurons. Importantly, my studies found that a specific
subset of CCAP-neurons, the CCAP-ENs, is both necessary and sufficient for ecdysis, and that
their function in ecdysis is mediated by extrinsic BMP-dependent peptide hormone expression.
Additionally, we found that the change in the ecdysis behavioral sequence from larval to pupal
ecdysis is supported by the recruitment of a ‘late’ subset of CCAP-neurons that are born in the
embryo but undergo extrinsic ecdysone-triggered, temporally-tuned differentiation immediately
prior to pupal ecdysis.Medicine, Faculty ofGraduat