Craniofacial development depends on cell-cell interactions, coordinated cellular movement and differentiation under the control of regulatory gene networks, which include the distal-less (Dlx) gene family. However, the functional significance of Dlx5 in patterning the oropharyngeal region has remained unknown. Here we show that loss of Dlx5 leads to a shortened soft palate and an absence of the levator veli palatini, palatopharyngeus, and palatoglossus muscles that are derived from the 4th pharyngeal arch (PA), but the tensor veli palatini, derived from the 1st PA, is unaffected. Dlx5-positive cranial neural crest (CNC) cells are in direct contact with myoblasts derived from the pharyngeal mesoderm, and Dlx5 disruption leads to altered proliferation and apoptosis of CNC and muscle progenitor cells. Moreover, the FGF10 pathway is downregulated in Dlx5-/- mice, and activation of FGF10 signaling rescues CNC cell proliferation and myogenic differentiation in these mutant mice. Collectively, our results indicate that Dlx5 plays critical roles in patterning of the oropharyngeal region and development of muscles derived from the 4th PA mesoderm in the soft palate, likely via interactions between CNC-derived and myogenic progenitor cells.
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RESEARCH ARTICLE|
01 January 2017
Dlx5-FGF10 signaling cascade controls cranial neural crest and myoblast interaction during oropharyngeal patterning and development
Hideki Sugii,
Hideki Sugii
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
2
Division of Endodontology, Kyushu University Hospital, Kyushu University, Fukuoka, Japan
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Alexandre Grimaldi,
Alexandre Grimaldi
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
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Jingyuan Li,
Jingyuan Li
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
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Carolina Parada,
Carolina Parada
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
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Thach Vu-Ho,
Thach Vu-Ho
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
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Jifan Feng,
Jifan Feng
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
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Junjun Jing,
Junjun Jing
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
3
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
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Yuan Yuan,
Yuan Yuan
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
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Yuxing Guo,
Yuxing Guo
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
4
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatological, Beijing 100081, China
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Hidefumi Maeda,
Hidefumi Maeda
2
Division of Endodontology, Kyushu University Hospital, Kyushu University, Fukuoka, Japan
5
Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
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Yang Chai
Yang Chai
*
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
*Author for correspondence:
2250 Alcazar Street – CSA 103, Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA
. ychai@usc.edu
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Hideki Sugii
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
2
Division of Endodontology, Kyushu University Hospital, Kyushu University, Fukuoka, Japan
Alexandre Grimaldi
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Jingyuan Li
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Carolina Parada
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Thach Vu-Ho
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Jifan Feng
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Junjun Jing
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
3
State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
Yuan Yuan
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
Yuxing Guo
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
4
Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatological, Beijing 100081, China
Hidefumi Maeda
2
Division of Endodontology, Kyushu University Hospital, Kyushu University, Fukuoka, Japan
5
Department of Endodontology and Operative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
Yang Chai
*
1
Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA 90033, USA
*Author for correspondence:
2250 Alcazar Street – CSA 103, Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA
. ychai@usc.edu
Received:
19 May 2017
Accepted:
21 Sep 2017
Online ISSN: 1477-9129
Print ISSN: 0950-1991
Development dev.155176.
Article history
Received:
19 May 2017
Accepted:
21 Sep 2017
Currently Viewing Accepted Manuscript - Newer Version Available
01 Nov 2017
Citation
Hideki Sugii, Alexandre Grimaldi, Jingyuan Li, Carolina Parada, Thach Vu-Ho, Jifan Feng, Junjun Jing, Yuan Yuan, Yuxing Guo, Hidefumi Maeda, Yang Chai; Dlx5-FGF10 signaling cascade controls cranial neural crest and myoblast interaction during oropharyngeal patterning and development. Development 2017; dev.155176. doi: https://doi.org/10.1242/dev.155176
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