Loss of Foxd4 Impacts Neurulation and Cranial Neural Crest Specification During Early Head Development.

Autor:	McMahon R; Embryology Research Unit, Children's Medical Research Institute, Sydney, NSW, Australia.; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Darlington, NSW, Australia., Sibbritt T; Embryology Research Unit, Children's Medical Research Institute, Sydney, NSW, Australia., Aryamanesh N; Embryology Research Unit, Children's Medical Research Institute, Sydney, NSW, Australia., Masamsetti VP; Embryology Research Unit, Children's Medical Research Institute, Sydney, NSW, Australia.; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Darlington, NSW, Australia., Tam PPL; Embryology Research Unit, Children's Medical Research Institute, Sydney, NSW, Australia.; School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Darlington, NSW, Australia.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2022 Feb 01; Vol. 9, pp. 777652. Date of Electronic Publication: 2022 Feb 01 (Print Publication: 2021).
DOI:	10.3389/fcell.2021.777652
Abstrakt:	The specification of anterior head tissue in the late gastrulation mouse embryo relies on signaling cues from the visceral endoderm and anterior mesendoderm (AME). Genetic loss-of-function studies have pinpointed a critical requirement of LIM homeobox 1 (LHX1) transcription factor in these tissues for the formation of the embryonic head. Transcriptome analysis of embryos with gain-of-function LHX1 activity identified the forkhead box gene, Foxd4, as one downstream target of LHX1 in late-gastrulation E7.75 embryos. Our analysis of single-cell RNA-seq data show Foxd4 is co-expressed with Lhx1 and Foxa2 in the anterior midline tissue of E7.75 mouse embryos, and in the anterior neuroectoderm (ANE) at E8.25 alongside head organizer genes Otx2 and Hesx1 . To study the role of Foxd4 during early development we used CRISPR-Cas9 gene editing in mouse embryonic stem cells (mESCs) to generate bi-allelic frameshift mutations in the coding sequence of Foxd4 . In an in vitro model of the anterior neural tissues derived from Foxd4 -loss of function (LOF) mESCs and extraembryonic endoderm cells, expression of head organizer genes as well as Zic1 and Zic2 was reduced, pointing to a need for FOXD4 in regulating early neuroectoderm development. Mid-gestation mouse chimeras harbouring Foxd4 -LOF mESCs displayed craniofacial malformations and neural tube closure defects. Furthermore, our in vitro data showed a loss of FOXD4 impacts the expression of cranial neural crest markers Twist1 and Sox9 . Our findings have demonstrated that FOXD4 is essential in the AME and later in the ANE for rostral neural tube closure and neural crest specification during head development. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 McMahon, Sibbritt, Aryamanesh, Masamsetti and Tam.)
Databáze:	MEDLINE
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