title: Satb2, modularity, and the evolvability of the vertebrate jaw.
abstract: Modularity is a key mechanism bridging development and evolution and is fundamental to evolvability. Herein, we investigate modularity of the Vertebrate jaw with the aim of understanding mechanisms of its morphological evolution. Conservation of the basic structural bauplan of Vertebrate jaws led to a Hinge and Caps model, in which polarity in the patterning system of developing jaws predicts modularity. We have tested the hypothesis that the Satb2+ cell population delineates a developmental module within the mandibular jaw. Satb2 is expressed in the mesenchyme of the jaw primordia that gives rise to distal elements of both the upper and lower jaws. Loss of Satb2 specifically affects structural elements of the distal (incisor) domain, reflecting the integration of these elements as well as their independence from other mandibular domains. Reducing Satb2 dosage leads to an increase in variation in mandibular length, providing insight into the developmental potential to generate variation. Inter-taxa comparisons reveal that the Satb2 domain is conserved within gnathostomes. We complement previous loss of function studies in mice with gene knock-down experiments in Xenopus, providing evidence for functional conservation of Satb2 in regulating size. Finally, we present evidence that the relative size of the amniote mandibular Satb2+ domain varies in relation to epithelial Fgf8 expression, suggesting a mechanism for evolutionary change in this domain. Taken together, our data support the Hinge and Caps model and provide evidence that Satb2 regulates coordinated distal jaw modules that are subject to evolutionary modification by signals emanating from the Hinge.
authors.affiliation: Department of Craniofacial Development, King's College, London, Guy's Hospital, London Bridge, London, UK.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Fish
authors.forename: Brian
authors.initials: B
authors.lastname: Villmoare
authors.forename: Katja
authors.initials: K
authors.lastname: Köbernick
authors.forename: Claudia
authors.initials: C
authors.lastname: Compagnucci
authors.forename: Olga
authors.initials: O
authors.lastname: Britanova
authors.forename: Victor
authors.initials: V
authors.lastname: Tarabykin
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Depew
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002645:Chickens; D051524:Fibroblast Growth Factor 8 / Q000235:genetics / Q000378:metabolism; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D014644:Genetic Variation; D008334:Mandible / Q000033:anatomy & histology / Q000196:embryology*; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008648:Mesoderm / Q000196:embryology; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D036961:Matrix Attachment Region Binding Proteins; D012333:RNA, Messenger; C501473:SATB2 protein, mouse; C555948:Satb2 protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins; D051524:Fibroblast Growth Factor 8