Cell-cell interaction determines cell fate of mesoderm-derived cell in tongue development through Hh signaling
- Division of Oral Anatomy, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Japan
- Center for Advanced Oral Science, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Japan
- Division of Orthodontics, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Japan
- Division of Oral Pathology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Japan
- Division of Dental Pharmacology, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Japan
- Centre for Craniofacial & Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, Guy’s Hospital, United Kingdom
- Service de Chirurgie Maxillofaciale et tomatology, Centre Hospitalier Universitaire de Nantes,1 place Alexis Ricordeau 44000, France
- Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy
- Medical Genetics, Department of Translational Medical Sciences, Federico II University of Naples, Italy, Italy
- Scuola Superiore Meridionale, School for Advanced Studies, Genomics and Experimental Medicine program,, Italy
Figures
Figure 1 with 3 supplements
Tongue phenotypes in Ofd1 mutant mice.
(A, B, E–H) Frontal sections showing histological images in wild-type (A, E, G), Ofd1fl;Wnt1Cre(HM) (B) and Ofd1fl/WT;Wnt1Cre(HET) (F–F’’, H) at embryonic day (E) 18.5. Arrow indicating sparse …
Figure 1—figure supplement 1
Abnormal shaped tongue in Ofd1fl/WT;Wnt1Cre(HET) mice.
Oral and frontal view of normal tongue in wild-type mice and abnormal shaped tongue in Ofd1fl/WT;Wnt1Cre(HET) mice.
Figure 1—figure supplement 2
Bone in tongue of Ofd1fl/WT;Wnt1Cre(HET) mice.
Frontal sections showing in situ hybridization of Runx2 (A, B) and histology (C, D) in wild-type (A, C) and Ofd1fl/WT;Wnt1Cre(HET) (B, D). Arrow and arrowhead indicating bone region and connection …
Figure 1—figure supplement 3
Tongue phenotypes in Ofd1fl/WT;Wnt1Cre(HET) mice.
Frontal section showing histological images of tongue in wild-type (A) and Ofd1fl/WT;Wnt1Cre(HET) mice (B) at embryonic day (E) 18.5. Scale bars: 200 µm (A, B).
Figure 2 with 4 supplements
Sparse tissue in Ofd1 mutant tongue.
(A–C) Quantitative PCR (q-PCR) on mRNA isolated from ectopic sparse tissue, white adipose tissue (WAT), and embryonic tongue muscle (ETM). Expression of white adipose maker (Agt) was examined to …
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Figure 2—source data 1
qPCR; Agt, UCP1 and PGC1a.
- https://cdn.elifesciences.org/articles/85042/elife-85042-fig2-data1-v1.xlsx
Figure 2—figure supplement 1
Quantitative PCR (q-PCR) and immunohistochemistry analysis (muscle and white adipose) on Ofd1fl/WT;Wnt1Cre(HET) mice.
(A) Myogenin (myogenic marker) was used to examine whether the sparse tissue was muscle. q-PCR of Myogenin on mRNA isolated from ectopic sparse tissue from Ofd1fl/WT;Wnt1Cre(HET) and embryonic …
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Figure 2—figure supplement 1—source data 1
qPCR; Myogenin and Trim13.
- https://cdn.elifesciences.org/articles/85042/elife-85042-fig2-figsupp1-data1-v1.xlsx
Figure 2—figure supplement 2
Quantitative PCR (q-PCR) and immunohistochemistry analysis (brown adipose) on Ofd1fl/WT;Wnt1Cre(HET) mice.
(A) Prdm16 (brown adipose marker) was used to examine whether the sparse tissue was brown adipose tissue. Frontal sections showing immunohistochemistry of Prdm16 in tongue of wild-type and Ofd1fl/WT;…
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Figure 2—figure supplement 2—source data 1
qPCR; UCP1 and Adiponectin.
- https://cdn.elifesciences.org/articles/85042/elife-85042-fig2-figsupp2-data1-v1.xlsx
Figure 2—figure supplement 3
Artifact and adipose tissue in wild-type tongue.
(A, B) Frontal sections showing empty spaces without surrounding cells in the tongue of prenatal (A) and postnatal (B) wild-type mice. Right panels are high magnification of left panels. Arrowheads …
Figure 2—figure supplement 4
Quantitative PCR (q-PCR) analysis (adipose) on Ofd1fl;Wnt1Cre(HM) mice.
q-PCR on mRNA isolated from ectopic sparse tissue of Ofd1fl;Wnt1Cre(HM), embryonic tongue muscle (ETM), and white adipose tissue (WAT). **p<0.01.
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Figure 2—figure supplement 4—source data 1
qPCR; Agt, Trim14 and Prdm16.
- https://cdn.elifesciences.org/articles/85042/elife-85042-fig2-figsupp4-data1-v1.xlsx
Figure 3 with 4 supplements
Interaction between cranial neural crest-derived cells (CNCC) and mesoderm-derived cells.
(A–D) Frontal images of YFP expression (A, B) and Myf5 expression of whole-mount in situ hybridization (C, D) in Mesp1Cre;R26RYFP (A), Wnt1Cre;R26RYFP (B), wild-type (C), and Ofd1fl;Wnt1Cre(HM) (D) …
Figure 3—figure supplement 1
Variation of Osr2-Cre activation.
Osr2-Cre activation (confirmed by LacZ staining in Osr2Cre;R26RLacZ) exhibited the three different patterns (Lan et al., 2007). Most embryos displayed tissue-specific pattern consistent with …
Figure 3—figure supplement 2
Osr2 expression in developing tongue.
(A) Frontal section showing LacZ stained Osr2Cre;R26RLacZ mice at embryonic day (E) 13.5. (B–G) Frontal sections showing in situ hybridization of Myf5 (A–C) and Osr2 (D–F) in anterior (A, D), middle …
Figure 3—figure supplement 3
Interaction between cranial neural crest-derived cells (CNCC) and mesoderm-derived cells.
Double immunohistochemistry of YFP and MyoD (A) and YFP and Prdm1 (B) on cultured YFP-expressing mesoderm-derived cells and YFP-negative CNCC obtained from Mesp1Cre;R26RYFP mice.
Figure 3—figure supplement 4
The cervical brown adipose tissue in Ofd1fl/WT;Wnt1Cre(HET) mice.
(A) Schematic diagram showing lateral view of supraclavicular (scBAT) and cervical (cBAT) brown adipose tissue. (B, C, F, G) Sagittal (B, C) and coronal (F, G) sections showing histology of scBAT …
Figure 4 with 1 supplement
X-inactivation in Ofd1 mutant tongue.
(A–E) Frontal sections showing immunohistochemistry of GFP (A–C) and MyoD (D, E) in Wnt1Cre(HET);Hprtfl (A), Ofd1fl;Wnt1Cre(HM);Hprtfl (B), Ofd1fl/WT;Wnt1Cre(HET);Hprtfl (C), wild-type (D), and Ofd1f…
Figure 4—figure supplement 1
Cluster of Ofd1 mutant cells in Ofd1fl/WT;Wnt1Cre(HET) mice.
Sagittal view of pharyngeal region of Wnt1Cre;Hprtfl (A) and Ofd1fl;Wnt1Cre(HET);Hprtfl (B). Arrowheads indicating cluster of GFP (-) cells.
Figure 5 with 2 supplements
Hh signal in Ofd1 mutant tongue.
(A–C’) Frontal sections showing in situ hybridization of Ptch1 in wild-type (A’), Ofd1fl;Wnt1Cre(HM) (B’), and Ofd1fl/WT;Wnt1Cre(HET) (C’) at embryonic day (E) 10. A, B, C, bright field …
Figure 5—figure supplement 1
Adipose in Smo mutant mice.
(A–D) Frontal section showing histological images of wild-type (A, C) and Smofl/fl;Osr2Cre(HM) (B, D) mice. B and D were high magnifications of A and C, respectively. (E–M) Quantitative PCR (q-PCR) …
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Figure 5—figure supplement 1—source data 1
qPCR; Myogenin, Cidea, C/EBPb, Prdm16, UCP1, PGC1a, Agt, Trim14 and Cidea.
- https://cdn.elifesciences.org/articles/85042/elife-85042-fig5-figsupp1-data1-v1.xlsx
Figure 5—figure supplement 2
Acetylated α-tubulin in cranial neural crest-derived cells (CNCC) during tongue development.
Frontal section showing immunohistochemistry of acetylated α-tubulin in YFP-expressing cells of Wnt1Cre(HET);R26RYfp (A) and Ofd1fl/WT;Wnt1Cre(HET);R26RYfp mice (B). CNCC were confirmed by YFP …
Figure 6 with 2 supplements
Hh signal in mesoderm-derived cells.
(A, B) Double immunohistochemistry of YFP and Ptch1 on cultured YFP-expressing cranial neural crest-derived cells (CNCC) accompanied by YFP-negative mesoderm-derived cells (A) and only YFP-negative …
Figure 6—figure supplement 1
Cyclopamine treated cranial neural crest-derived cells (CNCC) and mesoderm-derived cells.
Double immunohistochemistry of YFP and Ptch1 on cultured YFP-expressing CNCC accompanied by YFP-negative mesoderm-derived cells obtained from Wnt1Cre;R26RYFP mice with cyclopamine.
Figure 6—figure supplement 2
Apoptosis and cell proliferation in Ofd1 mutant tongue.
(A, B) Frontal sections showing Caspase-3 immunohistochemistry. (C) Comparison of the number of Caspase-3-positive cells between Wnt1Cre;R26RYFP mice and Ofd1fl;Wnt1Cre(HM);R26RYFP mice. (D, E) …
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Figure 6—figure supplement 2—source data 1
Percentage of Positive cells: Caspase-3 and Ki67.
- https://cdn.elifesciences.org/articles/85042/elife-85042-fig6-figsupp2-data1-v1.xlsx
Figure 7
Clefts in Ofd1 mutants.
(A, B) Oral (M) and frontal (N) view of Ofd1fl/WT;Wnt1Cre(HET) mice. Arrows indicating cleft. (C, D) Frontal (C) and sagittal (D) sections showing histological images. Blue and red arrows indicating …
Figure 8
Adipose tissue in Ofd1 mutant tongue.
(A, B, C–E’’) Frontal (A, B, D–E’’) and sagittal (C, C’) sections showing histological images in wild-type (D), and Ofd1fl/WT;Wnt1Cre(HET) (A–C’, E–E’’). E’ and E’’ are high magnification of E. (F, G…
Figure 9 with 1 supplement
Tongue in OFD1 patient.
(A, B) Tongue in OFD1 patient (G138S missense mutation). Arrowheads and arrows indicating protruded tissue and normal tongue, respectively. (C–L, O–R) Sections showing histological images (C–H, O, P)…
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Figure 9—source data 1
qPCR; UCP1.
- https://cdn.elifesciences.org/articles/85042/elife-85042-fig9-data1-v1.xlsx
Figure 9—figure supplement 1
Quantitative PCR (q-PCR) analysis on OFD1 patient tongue.
q-PCR of CIDEA (A), PGC1a (B), PRDM16 (C) and CIDEA (D) on mRNA isolated from ectopic sparse tissue from OFD1 patient tongue, cultured human myoblasts (CHM), and cultured human white adipocytes …
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Figure 9—figure supplement 1—source data 1
qPCR; CIDEA, PGC1a, PRDM16 and CIDEA.
- https://cdn.elifesciences.org/articles/85042/elife-85042-fig9-figsupp1-data1-v1.xlsx
Figure 10 with 1 supplement
Tongue frenum in Ofd1 mutant mice.
(A, B) Frontal sections showing in situ hybridization of Myf5 (A) and LacZ staining (B) in wild-type (A) and WntCre;R26RLacZ (B). Arrows indicating tongue frenum region. (C–E) Oral view of …
Figure 10—figure supplement 1
Tongue frenum formation in wild-type mice.
(A, B) Frontal section showing histological image (A) and in situ hybridization of Lgr5 (B) of tongue frenum (A) and mandible (B) in wild-type mice at embryonic day (E) 10.5 (B) and E12.5 (A). Arrow …
