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Delineating the roles of Grhl2 in craniofacial development through tissue‐specific conditional deletion and epistasis approaches in mouse
Author(s) -
Vries Michael,
Owens Harley G.,
Carpinelli Marina R.,
Partridge Darren,
Kersbergen Ariena,
Sutherland Kate D.,
Auden Alana,
Anderson Peter J.,
Jane Stephen M.,
Dworkin Sebastian
Publication year - 2021
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.322
Subject(s) - biology , neural crest , craniofacial , morphogenesis , endoderm , neural tube , haploinsufficiency , fate mapping , microbiology and biotechnology , ectoderm , genetics , embryogenesis , foregut , embryonic stem cell , phenotype , anatomy , embryo , gene
Background The highly conserved Grainyhead‐like ( Grhl ) family of transcription factors play critical roles in the development of the neural tube and craniofacial skeleton. In particular, deletion of family member Grainyhead‐like 2 ( Grhl2 ) leads to mid‐gestational embryonic lethality, maxillary clefting, abdominoschisis, and both cranial and caudal neural tube closure defects. These highly pleiotropic and systemic defects suggest that Grhl2 plays numerous critical developmental roles to ensure correct morphogenesis and patterning. Results Here, using four separate Cre‐lox conditional deletion models, as well as one genetic epistasis approach ( Grhl2 +/− ; Edn1 +/− double heterozygous mice) we have investigated tissue‐specific roles of Grhl2 in embryonic development, with a particular focus on the craniofacial skeleton. We find that loss of Grhl2 in the pharyngeal epithelium (using the Shh Cre driver) leads to low‐penetrance micrognathia, whereas deletion of Grhl2 within the ectoderm of the pharynx ( Nestin Cre ) leads to small, albeit significant, differences in the proximal‐distal elongation of both the maxilla and mandible. Loss of Grhl2 in endoderm ( Sox17‐2a iCre ) resulted in noticeable lung defects and a single instance of secondary palatal clefting, although formation of other endoderm‐derived organs such as the stomach, bladder and intestines was not affected. Lastly, deletion of Grhl2 in cells of the neural crest ( Wnt1 Cre ) did not lead to any discernible defects in craniofacial development, and similarly, our epistasis approach did not detect any phenotypic consequences of loss of a single allele of both Grhl2 and Edn1 . Conclusion Taken together, our study identifies a pharyngeal‐epithelium intrinsic, non‐cell‐autonomous role for Grhl2 in the patterning and formation of the craniofacial skeleton, as well as an endoderm‐specific role for Grhl2 in the formation and establishment of the mammalian lung.