No abstract

Phenotypic variation across mammals is extensive and reflects their ecological diversification into a remarkable range of habitats on every continent and in every ocean. The skull performs many functions to enable each species to thrive within its unique ecological niche, from prey acquisition, feeding, sensory capture (supporting vision and hearing) to brain protection. Diversity of skull function is reflected by its complex and highly variable morphology. Cranial morphology can be quantified using geometric morphometric techniques to offer invaluable insights into evolutionary patterns, ecomorphology, development, taxonomy, and phylogenetics. Therefore, the skull is one of the best suited skeletal elements for developmental and evolutionary analyses. In contrast, less attention is dedicated to the fibrous sutural joints separating the cranial bones. Throughout postnatal craniofacial development, sutures function as sites of bone growth, accommodating expansion of a growing brain. As growth frontiers, cranial sutures are actively responsible for the size and shape of the cranial bones, with overall skull shape being altered by changes to both the level and time period of activity of a given cranial suture. In keeping with this, pathological premature closure of sutures postnatally causes profound misshaping of the skull (craniosynostosis). Beyond this crucial role, sutures also function postnatally to provide locomotive shock absorption, allow joint mobility during feeding, and, in later postnatal stages, suture fusion acts to protect the developed brain. All these sutural functions have a clear impact on overall cranial function, development and morphology, and highlight the importance that patterns of suture development have in shaping the diversity of cranial morphology across taxa. Here we focus on the mammalian cranial system and review the intrinsic relationship between suture development and morphology and cranial shape from an evolutionary developmental biology perspective, with a view to understanding the influence of sutures on evolutionary diversity. Future work integrating suture development into a comparative evolutionary framework will be instrumental to understanding how developmental mechanisms shaping sutures ultimately influence evolutionary diversity.

Classical embryological experiments suggest that a posterior signal is required for patterning the developing anteroposterior axis. In this paper, we investigate a potential role for FGF signalling in this process. During normal development, embryonic fibroblast growth factor (eFGF) is expressed in the posterior of the Xenopus embryo. We have previously shown that overexpression of eFGF from the start of gastrulation results in a posteriorised phenotype of reduced head and enlarged proctodaeum. We have now determined the molecular basis of this phenotype and we propose a role for eFGF in normal anteroposterior patterning. In this study, we show that the overexpression of eFGF causes the up-regulation of a number of posteriorly expressed genes, and prominent among these are Xcad3, a caudal homologue, and the Hox genes, in particular HoxA7. There is both an increase of expression within the normal domains and an extension of expression towards the anterior. Application of eFGF-loaded beads to specific regions of gastrulae reveals that anterior truncations arise from an effect on the developing dorsal axis. Similar anterior truncations are caused by the dorsal overexpression of Xcad3 or HoxA7. This suggests that this aspect of the eFGF overexpression phenotype is caused by the ectopic activation of posterior genes in anterior regions. Further results using the dominant negative FGF receptor show that the normal expression of posterior Hox genes is dependent on FGF signalling and that this regulation is likely mediated by the activation of Xcad3. The biological activity of eFGF, together with its expression in the posterior of the embryo, make it a good candidate to fulfil the role of the ‘transforming’ activity proposed by Nieuwkoop in his ‘activation and transformation’ model for neural patterning.

LIM-homeobox containing (Lhx) genes encode trascriptional regulators which play critical roles in a variety of developmental processes. We have identified two genes belonging to a novel subfamily of mammalian Lhx genes, designated Lhx6 and Lhx7. Whole-mount in situ hybridisation showed that Lhx6 and Lhx7 were expressed during mouse embryogenesis in overlapping domains of the first branchial arch and the basal forebrain. More specifically, expression of Lhx6 and Lhx7 was detected prior to initiation of tooth formation in the presumptive oral and odontogenic mesenchyme of the maxillary and mandibular processes. During tooth formation, expression was restricted to the mesenchyme of individual teeth. Using explant cultures, we have shown that expression of Lhx6 and Lhx7 in mandibular mesenchyme was under the control of signals derived from the overlying epithelium; such signals were absent from the epithelium of the non-odontogenic second branchial arch. Furthermore, expression studies and bead implantation experiments in vitro have provided strong evidence that Fgf8 is primarily responsible for the restricted expression of Lhx6 and Lhx7 in the oral aspect of the maxillary and mandibular processes. In the telencephalon, expression of both genes was predominantly localised in the developing medial ganglionic eminences, flanking a Fgf8-positive midline region. We suggest that Fgf8 and Lhx6 and Lhx7 are key components of signalling cascades which determine morphogenesis and differentiation in the first branchial arch and the basal forebrain.

The molecular events of odontogenic induction are beginning to be elucidated, but until now nothing was known about the molecular basis of the patterning of the dentition. A role for Dlx-1 and Dlx-2 genes in patterning of the dentition has been proposed with the genes envisaged as participating in an ‘odontogenic homeobox gene code’ by specifying molar development. This proposal was based on the restricted expression of the genes in molar ectomesenchyme derived from cranial neural crest cells prior to tooth initiation. Mice with targeted null mutations of both Dlx-1 and Dlx-2 homeobox genes do not develop maxillary molar teeth but incisors and mandibular molars are normal. We have carried out heterologous recombinations between mutant and wild-type maxillary epithelium and mesenchyme and show that the ectomesenchyme underlying the maxillary molar epithelium has lost its odontogenic potential. Using molecular markers of branchial arch neural crest (Barx1) and commitment to chondrogenic differentiation (Sox9), we show that this population alters its fate from odontogenic to become chondrogenic. These results provide evidence that a subpopulation of cranial neural crest is specified as odontogenic by Dlx-1 and Dlx-2 genes. Loss of function of these genes results in reprogramming of this population of ectomesenchyme cells into chondrocytes. This is the first indication that the development of different shaped teeth at different positions in the jaws is determined by independent genetic pathways.