Abstract
BackgroundExpression of the mouse Delta-like 1 (Dll1) gene in the presomitic mesoderm and in the caudal halves of somites of the developing embryo is required for the formation of epithelial somites and for the maintenance of caudal somite identity, respectively. The rostro-caudal polarity of somites is initiated early on within the presomitic mesoderm in nascent somites. Here we have investigated the requirement of restricted Dll1 expression in caudal somite compartments for the maintenance of rostro-caudal somite polarity and the morphogenesis of the axial skeleton. We did this by overexpressing a functional copy of the Dll1 gene throughout the paraxial mesoderm, in particular in anterior somite compartments, during somitogenesis in transgenic mice.ResultsEpithelial somites were generated normally and appeared histologically normal in embryos of two independent Dll1 over-expressing transgenic lines. Gene expression analyses of rostro-caudal marker genes suggested that over-expression of Dll1 without restriction to caudal compartments was not sufficient to confer caudal identity to rostral somite halves in transgenic embryos. Nevertheless, Dll1 over-expression caused dysmorphologies of the axial skeleton, in particular, in morphological structures that derive from the articular joint forming compartment of vertebrae. Accordingly, transgenic animals exhibited missing or reduced intervertebral discs, rostral and caudal articular processes as well as costal heads of ribs. In addition, the midline of the vertebral column did not develop normally. Transgenic mice had open neural arches and split vertebral bodies with ectopic pseudo-growth plates. Endochondral bone formation and ossification in the developing vertebrae were delayed.ConclusionThe mice overexpressing Dll1 exhibit skeletal dysmorphologies that are also evident in several mutant mice with defects in somite compartmentalisation. The Dll1 transgenic mice demonstrate that vertebral dysmorphologies such as bony fusions of vertebrae and midline vertebral defects can occur without apparent changes in somitic rostro-caudal marker gene expression. Also, we demonstrate that the over-expression of the Dll1 gene in rostral epithelial somites is not sufficient to confer caudal identity to rostral compartments. Our data suggest that the restricted Dll1 expression in caudal epithelial somites may be particularly required for the proper development of the intervertebral joint forming compartment.
Highlights
Expression of the mouse Delta-like 1 (Dll1) gene in the presomitic mesoderm and in the caudal halves of somites of the developing embryo is required for the formation of epithelial somites and for the maintenance of caudal somite identity, respectively
The Dll1 transgenic mice demonstrate that vertebral dysmorphologies such as bony fusions of vertebrae and midline vertebral defects can occur without apparent changes in somitic rostro-caudal marker gene expression
We demonstrate that the over-expression of the Dll1 gene in rostral epithelial somites is not sufficient to confer caudal identity to rostral compartments
Summary
Expression of the mouse Delta-like 1 (Dll1) gene in the presomitic mesoderm and in the caudal halves of somites of the developing embryo is required for the formation of epithelial somites and for the maintenance of caudal somite identity, respectively. Each somite is divided in a rostral and caudal compartment with distinct gene expression and developmental fate [2,3,4] This R/C somite polarity is established early on in the presomitic mesoderm (PSM) prior to segmentation [5,6,7] and is essential for the subsequent resegmentation of sclerotomes [8,9] and the sequential patterning of the neural tube [10,11]. Experimental evidence suggests that Mesp and Notch signalling are required for the initiation of R/C somite compartmentalisation in nascent somites through induction and suppression of Dll expression in caudal and rostral somite halves, respectively [12,13,14]. The maintenance of somite R/C polarity requires the compartmentalised expression of caudal genes, such as Dll, Notch, Paraxis and Uncx4.1 [15]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
