TY - JOUR
T1 - The DLx5-FGF10 signaling cascade controls cranial neural crest and myoblast interaction during oropharyngeal patterning and development
AU - Sugii, Hideki
AU - Grimaldi, Alexandre
AU - Li, Jingyuan
AU - Parada, Carolina
AU - Vu-Ho, Thach
AU - Feng, Jifan
AU - Jing, Junjun
AU - Yuan, Yuan
AU - Guo, Yuxing
AU - Maeda, Hidefumi
AU - Chai, Yang
N1 - Funding Information:
We are grateful to Dr Julie Mayo and Dr Bridget Samuels for critical reading and editing of the manuscript. We thank Dr John Rubenstein at UCSF for Dlx5 mutant mice, Vasu Punj for analyses of RNA-seq and USC Norris Medical Library Bioinformatics Service for assisting with data analysis. The bioinformatics software and computing resources used in the analysis are funded by USC Office of Research and the Norris Medical Library.
Funding Information:
This work was supported by the National Institute of Dental and Craniofacial Research (National Institutes of Health) (R37 DE012711 and U01 DE024421 to Y.C.). Deposited in PMC for release after 12 months.
Publisher Copyright:
© 2017. Published by The Company of Biologists Ltd.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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); however, 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 crucial roles in the 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.
AB - 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); however, 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 crucial roles in the 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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U2 - 10.1242/dev.155176
DO - 10.1242/dev.155176
M3 - Article
C2 - 28982687
AN - SCOPUS:85032835313
VL - 144
SP - 4037
EP - 4045
JO - Journal of Embryology and Experimental Morphology
JF - Journal of Embryology and Experimental Morphology
SN - 0950-1991
IS - 21
ER -