I am thrilled to share the culmination of my undergrad work (my 1st paper!) is now available via @Dev_Bio_Journal. We studied existing and novel mouse models of #SpinaBifida to study how neuronal migration into the pelvic ganglia alters urination in patients with this disease. 1/
We showed that by mid-gestation in mice with Pax3 mutant spina bifida, the pelvic ganglia that innervate the bladder were severely underdeveloped with significantly reduced area, neural density, and proliferation. 3/
By comparing neuronal subtypes in the ganglia between our #SpinaBifida models, we were able to demonstrate that Pax3 expression in non-neural crest cells is responsible for differentiation into CGRP+ neurons. Only constitutive mutants showed complete absence of these neurons. 4/
We showed that CGRP+ innervation of the bladder is severely reduced in constitutive Pax3 homozygous mutants. Additionally, neurons projected a shorter distance into the bladder in mutants as compared to WT littermates. This replicates bladder findings in patients. 5/
Because mouse models of #SpinaBifida often die shortly after birth, it is difficult to study many of the lifelong complications that affect patients, like overactive bladder. By time- and lineage-restricting the causative Pax3 mutation, our mice survived up to 6 weeks of age. 6/
We measured urination behaviors in lineage-restricted Pax3 mutants to understand the contributions of NCC to the urge to urinate using the Void Spot Assay. Interestingly, urination behaviors were altered only in lineage-restricted mutant males. 7/
Lastly, consistent with our functional results, we found that all postnatal male mutants and some females exhibited diminished bladder wall innervation. 8/
I am infinitely thankful to @MSouthardSmith for allowing me to work on this project and for introducing me to developmental genetics! I'm excited to further understanding of developmental and pediatric diseases throughout my career. Cheers to being a published author!! 🥳🍾 9/9
You can follow @makenziebeaman.
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