Dr. Natasha Shylo-Morphological changes and two Nodal paralogs drive left-right asymmetry in the squamate veiled chameleon; Dr. Nicole Edwards-Discovering the developmental basis of trachea-esophageal birth defects: evidence for endosomeopathies.

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• Dr. Natasha Shylo, Stowers Institute for Medical Research & Dr. Nicole Edwards, Cincinnati Children's Hospital Medical Center
• Monday 16 October 2023, 14:30-15:30
• Online.

If you have a question about this talk, please contact Jia CHEN.

Natasha Shylo

Morphological changes and two Nodal paralogs drive left-right asymmetry in the squamate veiled chameleon (Chamaeleo calyptratus).

The ancestral mode of left-right (L-R) patterning in deuterostomes involves motile cilia in the L-R organizer (LRO). However, avians and some mammals have lost motile cilia in their LRO and establish L-R asymmetry through asymmetric cell movements. Currently, the exact mechanism regulating L-R patterning in non-avian reptiles remains an enigma, since at the time of oviposition most squamate embryos are well into organogenesis. Veiled chameleon embryos are pre-gastrula at oviposition, making them an excellent organism for studying early development and evolution of the 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 two paralogs of Nodal in the left lateral plate mesoderm (LPM) albeit in non-identical patterns. The extent of Nodal signaling is constrained by Cer1, which is enriched in the left LPM , and Lefty which although absent from the LPM , has retained its midline barrier function through enrichment on the left side of the notochord. Shh is expressed symmetrically between the left and right sides of the floor plate but reveals a surprising morphological asymmetry within the embryo. Through live imaging we observe a leftward tilt in the posterior neural plate hinge point, and this morphological L-R asymmetry precedes, and likely triggers, asymmetric expression of the Nodal cascade. Furthermore, the L-R morphological changes occurring in the embryo temporally align with changes in the neural plate morphology. Future studies will therefore mechanistically compare the patterns of asymmetric cell movement in veiled chameleons to avian reptiles, and in concert with a newly annotated genome, I will perform gene editing in chameleons to study non-LRO roles for cilia in L-R patterning. Thus, chameleons provide a unique evolutionary and biomedical model for studying L-R patterning.

Nicole Edwards

Discovering the developmental basis of trachea-esophageal birth defects: evidence for endosomeopathies.

One in 3000 children are born with life threatening structural birth defects affecting 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 embryonic development is not well understood. By whole genome sequencing of patient-parent trios, we have discovered an enrichment of risk genes associated with endosome trafficking pathways, suggesting that endosome-mediated epithelial remodeling is a common molecular pathway disrupted in trachea-esophageal birth defects. We show that mutating core endosome pathway proteins in Xenopus causes trachea-esophageal separation defects due to disrupted trafficking of polarity proteins in the remodeling trachea-esophageal epithelium. 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 endosomeopathies: mutation of genes involved in endosome trafficking causes multi-organ defects including trachea-esophageal anomalies.

This talk is part of the Morphogenesis Seminar Series series.

This talk is included in these lists:

• Graduate-Seminars
• Morphogenesis Seminar Series
• Online

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