The mesenchymal architecture of the cranial mesoderm of mouse embryos is disrupted by the loss of Twist1 function

Abstract

The basic helix-loop-helix transcription factor Twist1 is a key regulator of craniofacial development. Twist1-null mouse embryos exhibit failure of cephalic neural tube closure and abnormal head development and die at E11.0. To dissect the function of Twist1 in the cranial mesoderm beyond mid-gestation, we used Mesp1-Cre to delete Twist1 in the anterior mesoderm, which includes the progenitors of the cranial mesoderm. Deletion of Twist1 in mesoderm cells resulted in loss and malformations of the cranial mesoderm-derived skeleton. Loss of Twist1 in the mesoderm also resulted in a failure to fully segregate the mesoderm and the neural crest cells, and the malformation of some cranial neural crest-derived tissues. The development of extraocular muscles was compromised whereas the differentiation of branchial arch muscles was not affected, indicating a differential requirement for Twist1 in these two types of craniofacial muscle. A striking effect of the loss of Twist1 was the inability of the mesodermal cells to maintain their mesenchymal characteristics, and the acquisition of an epithelial-like morphology. Our findings point to a role of Twist1 in maintaining the mesenchyme architecture and the progenitor state of the mesoderm, as well as mediating mesoderm-neural crest interactions in craniofacial development.

Osterix/Sp7 limits cranial bone initiation sites and is required for formation of sutures

“…While the Msx genes are thought to promote osteoblast differentiation, Twist genes are thought to favor maintenance of undifferentiated mesenchymal cells (Bildsoe et al, 2013; Han et al, 2007; Isenmann et al, 2009; Ishii et al, 2003). Therefore, we examined expression of all members of these gene families in zebrafish (four twist genes and five msx genes) by in situ hybridization on sections through the coronal suture, in WT and sp7 mutant fish.…”

Extraocular Muscle Repair and Regeneration

“…These include Twist1, whose absence results in compromised development of the EOMs [35]. Absence of Twist1 causes abnormalities in neural crest functional development [36].…”

Context-specific function of the LIM homeobox 1 transcription factor in head formation of the mouse embryo

“…To inactivate Lhx1 flox in the mesoderm, we used a Cre recombinase that is expressed from the Mesp1 locus (Saga et al, 1999). Mesoderm cells that express Mesp1-Cre have been shown to contribute extensively to the cranial mesenchyme (Saga et al, 1999;Bildsoe et al, 2013). In the mesoderm conditional mutant (Lhx1 flox/− ; Mesp1 +/Cre , hereafter Lhx1-mesCKO) embryos, Lhx1 expression was detected initially in the nascent mesoderm adjacent to the primitive streak (supplementary material Fig.…”