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Signaling networks in palate development

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Palatogenesis, the formation of the palate, is a dynamic process regulated by a complex series of context‐dependent morphogenetic signaling events. Many genes involved in palatogenesis have been discovered through the use of genetically manipulated mouse models as well as from human genetic studies, but the roles of these genes and their products in signaling networks regulating palatogenesis are still poorly known. In this review, we give a brief overview on palatogenesis and introduce key signaling cascades leading to formation of the intact palate. Moreover, we review conceptual differences between pathway biology and network biology and discuss how some of the recent technological advances in conjunction with mouse genetic models have contributed to our understanding of signaling networks regulating palate growth and fusion. This article is categorized under: Biological Mechanisms > Cell Signaling Developmental Biology > Developmental Processes in Health and Disease Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models

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Schematic representation of palatal growth and fusion. Palatal shelves (PS) can be first seen as outgrowths of the maxillary processes of the first pharyngeal arch (E11.5). Then they grow vertically down along the sides of the tongue (T; E13.0), rapidly elevate (E14.0), form a contact with each other and with the nasal septum (NS) in the anterior palate (P) (E15.0), and eventually fuse (E16.0).
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Schematic comparison of a pathway biology model (a) to a network biology model (b). Arrows depict interactions between signaling molecules. In a pathway biology model (a), genomic information regulating a cell fate is mediated by a linear pathway, where every downstream function is directly affected by an upstream signaling molecule. In a network biology model (b), genomic information controlling a certain cell fate is mediated by a network of interacting molecules.
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(a) Molecular control of palatal epithelial (green) differentiation. Fgf‐Notch signaling, P63‐Irf6 signaling, Tbx1, and Ikk‐α regulate differentiation or the prefusion palatal epithelium (green). (b) Medial edge epithelial loss is mediated via a signaling cascade involving TGF‐β3, Irf6, p63, and p21in the palatal midline epithelial seam (green).
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Signaling circuits governing palatal shelf growth and patterning. (a) Epithelial–mesenchymal interactions via Pax9‐regulated Shh‐Bmp and Shh‐Fgf feedback loops control growth and patterning of the anterior palate. (b) Oro‐nasal patterning of the anterior secondary palate is regulated via Fgf7‐mediated Shh repression. (c) Pax9‐regulated expression of Bmp4 and Osr2 in the posterior palatal mesenchyme and Shh in the posterior palatal epithelium is required for appropriate posterior growth of the secondary palate. In addition, Meox2, Barx1, and Mn1‐Tbx22 signaling module regulate posterior palatal growth. Gray, palatal mesenchyme; Green, palatal epithelium.
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Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
Biological Mechanisms > Cell Signaling
Developmental Biology > Developmental Processes in Health and Disease

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