The Molecular Origins of Species-Specific Facial Pattern

Samantha A. Brugmann; Minal D. Tapadia; Jill A. Helms    Department of Plastic and Reconstructive Surgery, Stanford University, Stanford, California 94305

I Introduction

Throughout the millennia, mankind has pondered how the enormous variation in animal form has come into existence. From Owen's concept of a “vertebrate archetype” that served as the foundation on which morphological diversity is generated, to Darwin's theory of evolution, we have been puzzling over the question of how diversity in the Animal Kingdom comes about. Our interest in obtaining answers to this age-old riddle has only increased in the intervening decades since these famous scientists debated the topic. In fact, one might summarize the objective of most current research in developmental and evolutionary biology as having a single goal: to understand the process by which shape and form (i.e., morphogenesis) is regulated. In this chapter, our primary goal is to describe recent study that provides clues into the molecular origins of species-specific craniofacial morphogenesis.

We have focused on growth and patterning of the craniofacial complex as a model for species diversity for three reasons. The first rationale is that, despite the fact that animals have such different looking faces, the general organization of vertebrate craniofacial complex is remarkably similar during early embryonic development. This suggests that a fundamental set of patterning genes might initially define the global organization of the facial prominences. From this conserved pattern, the widely divergent variations in facial form might then arise, from the gentle spatiotemporal tweaking of the expression of common genes.

The second reason we have focused on the face as a model system is that the craniofacial region exhibits such extraordinary variation in form, and these variations are closely associated with adaptive radiations into new ecological niches. A prime example is the Galapagos finches, where the principal intraspecies variation is the size and shape of their facial prominences (in birds, facial prominences such as beaks). Thus we propose that understanding the mechanisms regulating craniofacial morphogenesis in any species holds the potential to understand, at both molecular and cellular levels, the basis for evolutionary diversity.

A third motivation to focus on craniofacial patterning as a window into species-specific morphology is that there are a great number of anatomical landmarks that serve as species-specific characteristics. For example, the dentition was a feature of vertebrates but about 150 million years ago, birds lost this characteristic while mammals retained it. Even within the dentition itself, there are species-specific features: some mammals do not form premolar teeth whereas others (humans included) do. Because of these inherent species-specific differences we can begin to ask questions such as how a particular characteristic (in this case, teeth) might be retained or lost, or how a trait may be modified in such a way to ideally suit an animal. Although the mechanisms responsible for such species-specific morphological differences are still to be discovered, a growing number of studies now show that some answers to these age-old puzzles are within our grasp.

A Organization of the Face

Although the vertebrate head exhibits an exceedingly intricate and varied morphology, by the time an animal is born the craniofacial complex from which it arises initially has a much more simple geometry. This arrangement consists of a series of swellings or prominences that undergo fusion and expansion in an orderly and integrated fashion (Fig. 1A–D). There are seven prominences that comprise the vertebrate face: the midline frontonasal prominence, and three paired structures, the lateral nasal, maxillary, and mandibular prominences, which are derived from the first pharyngeal (branchial) arch. The frontonasal prominence contributes to the forehead, middle of the nose, philtrum of the upper lip, and primary palate. The lateral nasal prominence forms the sides of the nose; the maxillary prominences contribute to the sides of the face, lips and the secondary palate; the mandibular prominences produce the lower jaw (Fig. 1E).

The maxillary and mandibular prominences are derived from a single arch, hence one might wonder just how early on in the ontogeny of the craniofacial complex do cells irreversibly segregate into “maxillary” and “mandibular” subdivisions. That question was recently addressed when two groups of investigators considered this issue from an evolutionary perspective. The question of interest was the extent to which cells destined to occupy the maxillary portion of the first arch were separated from those cells bound to take up residence in the mandibular portion of the first arch. The groups independently examined the contributions of first arch neural crest cells to the maxillary process, in axolotl and chick and found that structures believed to be derived from maxillary condensation (i.e., Meckel's cartilage and the palatoquadrate) are solely derived from the mandibular condensation. Further, these fate-mapping studies proved that the maxillary process and its skeletal derivatives (the trabecular cartilage) are not derived from the first pharyngeal arch but rather from a condensation located between the eye and the maxillo-mandibular cleft (Cerny et al., 2004; Lee et al., 2004). One might wonder why such information is crucial to the study of craniofacial biology; simply put, when we know the origins of a structure we also gain knowledge about the origins of developmental anomalies affecting that structure. With this in mind, we begin this chapter by exploring new advances into the earliest events in facial patterning.

II Molecular and Tissue Interactions that Regulate Craniofacial Patterning

As might be deduced from the initial description of craniofacial morphogenesis, the process by which the face forms requires an elaborate series of intricately linked morphological events involving cell proliferation, differentiation,...