Michael J. Depew

Historically, examinations of gnathostome skulls have indicated that for essentially the entirety of their existence, jaws have been characterized by a high degree of fidelity to an initial basic structural design that will then go on to manifest an amazing array of end‐point phenotypes. These two traits—bauplan fidelity and elaboration of design—are inter‐connected and striking, and beg a number of questions, including: Are all jaws made in the same manner and if not how not? To begin to tackle such questions, we herein operationally define jaws as two appositional, hinged cranial units for which polarity and potential modularity are characteristics, and then address what is necessary for them to form, including delineating both the sources of cells and tissues that will formally yield the jaws as well as what informs their ontogeny (e.g., sources of positional information and factors directing the interpretation of developmental cues). Following on this, we briefly describe a predictive, testable model of jaw development (the “Hinge and Caps” model) and present evidence that theSatb2+cell population in the developing jaw primordia of mice defines a developmentally and evolutionarily significant jaw module such as would be predicted by the model.J. Exp. Zool. (Mol. Dev. Evol.) 310B:315–335, 2008.

Classic neontology (comparative embryology and anatomy), through the application of the concept of homology, has demonstrated that the development of the gnathostome (jawed vertebrate) skull is characterized both by a fidelity to the gnathostome bauplan and the exquisite elaboration of final structural design. Just as homology is an old concept amended for modern purposes, so are many of the questions regarding the development of the skull. With due deference to Geoffroy‐St. Hilaire, Cuvier, Owen, Lankester et al., we are still asking: How are bauplan fidelity and elaboration of design maintained, coordinated, and modified to generate the amazing diversity seen in cranial morphologies? What establishes and maintains pattern in the skull? Are there universal developmental mechanisms underlying gnathostome autapomorphic structural traits? Can we detect and identify the etiologies of heterotopic (change in the topology of a developmental event), heterochronic (change in the timing of a developmental event), and heterofacient (change in the active capacetence, or the elaboration of capacity, of a developmental event) changes in craniofacial development within and between taxa? To address whether jaws are all made in a like manner (and if not, then how not), one needs a starting point for the sake of comparison. To this end, we present here a “hinge and caps” model that places the articulation, and subsequently the polarity and modularity, of the upper and lower jaws in the context of cranial neural crest competence to respond to positionally located epithelial signals. This model expands on an evolving model of polarity within the mandibular arch and seeks to explain a developmental patterning system that apparently keeps gnathostome jaws in functional registration yet tractable to potential changes in functional demands over time. It relies upon a system for the establishment of positional information where pattern and placement of the “hinge” is driven by factors common to the junction of the maxillary and mandibular branches of the first arch and of the “caps” by the signals emanating from the distal‐most first arch midline and the lamboidal junction (where the maxillary branch meets the frontonasal processes). In this particular model, the functional registration of jaws is achieved by the integration of “hinge” and “caps” signaling, with the “caps” sharing at some critical level a developmental history that potentiates their own coordination. We examine the evidential foundation for this model in mice, examine the robustness with which it can be applied to other taxa, and examine potential proximate sources of the signaling centers. Lastly, as developmental biologists have long held that the anterior‐most mesendoderm (anterior archenteron roof or prechordal plate) is in some way integral to the normal formation of the head, including the cranial skeletal midlines, we review evidence that the seminal patterning influences on the early anterior ectoderm extend well beyond the neural plate and are just as important to establishing pattern within the cephalic ectoderm, in particular for the “caps” that will yield medial signaling centers known to coordinate jaw development. Developmental Dynamics 235:1256–1291, 2006.

The branchial arches are meristic vertebrate structures, being metameric both between each other within the rostrocaudal series along the ventrocephalic surface of the embryonic head and within each individual arch: thus, just as each branchial arch must acquire a unique identity along the rostrocaudal axis, each structure within the proximodistal axis of an arch must also acquire a unique identity. It is believed that regional specification of metameric structures is controlled by the nested expression of related genes resulting in a regional code, a principal that is though to be demonstrated by the regulation of rostrocaudal axis development in animals exerted by the nestedHOM‐C/Hoxhomeobox genes. The nested expression pattern of theDlxgenes within the murine branchial arch ectomesenchyme has more recently led to the proposal of aDlxcode for the regional specification along the proximodistal axis of the branchial arches (i.e. it establishes intra‐arch identity). This review re‐examines this hypothesis, and presents new work on an allelic series ofDlxloss‐of‐function mouse mutants that includes various combinations ofDlx1,Dlx2,Dlx3,Dlx5andDlx6. Although we confirm fundamental aspects of the hypothesis, we further report a number of novel findings. First, contrary to initial reports,Dlx1,Dlx2andDlx1/2heterozygotes exhibit alterations of branchial arch structures andDlx2^–/–andDlx1/2^–/–mutants have slight alterations of structures derived from the distal portions of their branchial arches. Second, we present evidence for a role for murineDlx3in the development of the branchial arches. Third, analysis of compoundDlxmutants reveals four grades of mandibular arch transformations and that the genetic interactions ofcisfirst‐order (e.g.Dlx5andDlx6),transsecond‐order (e.g.Dlx5andDlx2) andtransthird‐order paralogues (e.g.Dlx5andDlx1) result in significant and distinct morphological differences in mandibular arch development. We conclude by integrating functions of theDlxgenes within the context of a hypothesized general mechanism for the establishment of pattern and polarity in the first branchial arch of gnathostomes that includes regionally secreted growth factors such asFgf8andBmpand other transcription factors such asMsx1, and is consistent both with the structure of the conserved gnathostome jaw bauplan and the elaboration of this bauplan to meet organismal end‐point designs.