Cilia-mediated Hedgehog signaling controls form and function in the mammalian larynx

  1. Jacqueline M Tabler
  2. Maggie M Rigney
  3. Gordon J Berman
  4. Swetha Gopalakrishnan
  5. Eglantine Heude
  6. Hadeel Adel Al-lami
  7. Basil Z Yannakoudiadkis
  8. Rebecca D Fitch
  9. Christopher Carter
  10. Steven Vokes
  11. Karen J Liu
  12. Shahragim Tajbakhsh
  13. SE Roian Egnor
  14. John B Wallingford  Is a corresponding author
  1. University of Texas at Austin, United States
  2. Emory University, United States
  3. Institut Pasteur, France
  4. King’s College London, United Kingdom
  5. Howard Hughes Medical Institute, United states
9 figures

Figures

Anatomy of the mouse larynx.

(A) Diagram representing ventral view of mouse laryngeal anatomy. Dashed lines indicate sectional plane represented in panels C–F. (B) Ventral view of an excised adult larynx stained with alcian …

https://doi.org/10.7554/eLife.19153.003
Figure 2 with 2 supplements
Laryngeal anatomy is disrupted in Fuz and Gli3 mutants.

(A–C) H and E staining of horizontal sections of E18.5 larynges. (A’–C’) Diagrams of anatomy shown in (A–C). Fuz mutant larynges (B–B’) are significantly altered compared to controls, (A–A’). …

https://doi.org/10.7554/eLife.19153.004
Figure 2—figure supplement 1
Fgf8 reduction in Fuz mutants partially rescues laryngeal phenotypes.

(A) Diagram indicating sectional plane of E16.5 embryos. (B–C) Trichrome staining of frontal E16.5 Fuz+/+; Fgf8Lacz/+ (B), Fuz+/+(C), and Fuz-/-; Fgf8Lacz/+ embryos. (B’–C’) Diagrams illustrating …

https://doi.org/10.7554/eLife.19153.005
Figure 2—figure supplement 2
Wnt1Cre driven deletion of Fuz does not affect laryngeal morphology.

(A–B) H&E staining of horizontal sections E16.5 larynges in FuzFl/+; Wnt1Cre/+(A) and FuzFl/+; Wnt1Cre/+ (B) embryos.

https://doi.org/10.7554/eLife.19153.006
Thyroid cartilage and vocal ligament are mostly neural crest derived.

(A) Diagram representing anatomy in (B–B’). (B–B’) Horizontal section of rostral E18.5 Wnt1Cre/+; R26mTmGlarynx. Neural crest derivatives are labeled in green while other tissues are labeled with …

https://doi.org/10.7554/eLife.19153.007
Vocal fold muscles are from cranial mesodermal origin.

(A) Horizontal section of rostral E18.5 Mesp1Cre; R26Tomatolarynx showing that the arytenoid and cricoid cartilages, and Desmin-positive vocal fold muscles are derived from mesoderm. (B) Horizontal …

https://doi.org/10.7554/eLife.19153.008
Neural crest is expanded in Fuz and Gli3 mutant larynges.

(A–C) Horizontal section of E14.25 larynges. (A) Wild Type Wnt1Cre::mGFP labeled larynx (B) Fuz-/-; Wnt1Cre/+; R26mTmG larynx. (C) Gli3-/-;Wnt1Cre/+; R26mTmG. Neural crest is labeled in green and …

https://doi.org/10.7554/eLife.19153.009
Expanded Thyroglottal connective tissue in Gli3 mutants is neural crest derived.

(A–C) Horizontal sections of the E18.5 ventral larynx in Gli3+/+;Wnt1Cre/+; R26mTmG(A) Gli3+/-;Wnt1Cre/+; R26mTmG (B) Gli3-/-;Wnt1Cre/+; R26mTmG(C) embryos. (A’–C’) Diagrams representing anatomy …

https://doi.org/10.7554/eLife.19153.010
Gli3 mutant laryngeal morphology is significantly altered.

(A) Diagram representing laryngeal measurement presented in (B–F). (B) Quantification of total laryngeal cross sectional area excluding extrinsic muscles in E18.5 Gli3+/+ (n = 5), Gli3+/- (n = 5), Gl…

https://doi.org/10.7554/eLife.19153.011
WT and HT vocalizations do not differ on simple acoustic measures.

(A) Examples of Gli3+/- vocalizations with (top panel) and without (bottom panel) frequency steps. (B) Examples of Gli3+/- vocalizations with (top panel) and without (bottom panel) frequency steps. …

https://doi.org/10.7554/eLife.19153.012
Map of pup vocal repertoire reveals differences in acoustic structure.

(A) Position of each vocalization within the vocal repertoire map (Individual vocalizations). To generate the map, we defined the difference between two vocalizations to be the dynamically …

https://doi.org/10.7554/eLife.19153.013

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