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SUMMARY:Dr. Natasha Shylo-Morphological changes and two Nodal paralogs dri
 ve left-right asymmetry in the squamate veiled chameleon\; Dr. Nicole Edwa
 rds-Discovering the developmental basis of trachea-esophageal birth defect
 s: evidence for endosomeopathies. - Dr. Natasha Shylo\, Stowers Institute 
 for Medical Research & Dr. Nicole Edwards\, Cincinnati Children's Hospital
  Medical Center
DTSTART:20231016T133000Z
DTEND:20231016T143000Z
UID:TALK206212@talks.cam.ac.uk
CONTACT:Jia CHEN
DESCRIPTION:Natasha Shylo \n\nMorphological changes and two Nodal paralogs
  drive left-right asymmetry in the squamate veiled chameleon (Chamaeleo ca
 lyptratus). \n\nThe ancestral mode of left-right (L-R) patterning in deute
 rostomes involves motile cilia in the L-R organizer (LRO). However\, avian
 s and some mammals have lost motile cilia in their LRO and establish L-R a
 symmetry through asymmetric cell movements. Currently\, the exact mechanis
 m regulating L-R patterning in non-avian reptiles remains an enigma\, sinc
 e at the time of oviposition most squamate embryos are well into organogen
 esis. Veiled chameleon embryos are pre-gastrula at oviposition\, making th
 em an excellent organism for studying early development and evolution of t
 he molecular and cellular mechanisms governing L-R patterning. Like avians
 \, geckos and turtles\, chameleons lack motile cilia in the L-R organizer.
  However\, contrary to those reptiles\, chameleons exhibit expression of t
 wo paralogs of Nodal in the left lateral plate mesoderm (LPM) albeit in no
 n-identical patterns. The extent of Nodal signaling is constrained by Cer1
 \, which is enriched in the left LPM\, and Lefty which although absent fro
 m the LPM\, has retained its midline barrier function through enrichment o
 n the left side of the notochord. Shh is expressed symmetrically between t
 he left and right sides of the floor plate but reveals a surprising morpho
 logical asymmetry within the embryo. Through live imaging we observe a lef
 tward tilt in the posterior neural plate hinge point\, and this morphologi
 cal L-R asymmetry precedes\, and likely triggers\, asymmetric expression o
 f the Nodal cascade. Furthermore\, the L-R morphological changes occurring
  in the embryo temporally align with changes in the neural plate morpholog
 y. Future studies will therefore mechanistically compare the patterns of a
 symmetric cell movement in veiled chameleons to avian reptiles\, and in co
 ncert with a newly annotated genome\, I will perform gene editing in chame
 leons to study non-LRO roles for cilia in L-R patterning. Thus\, chameleon
 s provide a unique evolutionary and biomedical model for studying L-R patt
 erning. \n\nNicole Edwards \n\nDiscovering the developmental basis of trac
 hea-esophageal birth defects: evidence for endosomeopathies.\n\nOne in 300
 0 children are born with life threatening structural birth defects affecti
 ng the trachea and esophagus. Trachea-esophageal birth defects are caused 
 by spontaneous genetic mutations. However\, many cases have no identified 
 causative risk gene\, and how the trachea and esophagus form during embryo
 nic development is not well understood. By whole genome sequencing of pati
 ent-parent trios\, we have discovered an enrichment of risk genes associat
 ed with endosome trafficking pathways\, suggesting that endosome-mediated 
 epithelial remodeling is a common molecular pathway disrupted in trachea-e
 sophageal birth defects. We show that mutating core endosome pathway prote
 ins in Xenopus causes trachea-esophageal separation defects due to disrupt
 ed trafficking of polarity proteins in the remodeling trachea-esophageal e
 pithelium. We also observed disrupted polarity in Xenopus mutants of novel
  patient variants in genes predicted to function in endocytosis. Together\
 , our results implicate a genetic and developmental basis for endosomeopat
 hies: mutation of genes involved in endosome trafficking causes multi-orga
 n defects including trachea-esophageal anomalies. 
LOCATION:Online
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