Embryonic Submandibular Gland Morphogenesis: Stage-Specific Protein Localization of FGFs, BMPs, Pax6 and Pax9 in Normal Mice and Abnormal SMG Phenotypes in <i>FgfR2-IIIc^+/Δ</i>, <i>BMP7^–/–</i> and <i>Pax6^–/–</i>Mice

Abstract

Embryonic submandibular salivary gland (SMG) initiation and branching morphogenesis are dependent on cell-cell communications between and within epithelium and mesenchyme. Such communications are typically mediated in other organs (teeth, lung, lacrimal glands) by growth factors in such a way as to translate autocrine, juxtacrine and paracrine signals into specific gene responses regulating cell division and histodifferentiation. Using Wnt1-Cre/R26R transgenic mice, we demonstrate that embryonic SMG mesenchyme is derived exclusively from cranial neural crest. This origin contrasts to that known for tooth mesenchyme, previously shown to be derived from both neural crest and nonneural crest cells. Thus, although both SMGs and teeth are mandibular derivatives, we can expect overlap and differences in the details of their early inductive interactions. In addition, since embryonic SMG branching morphogenesis is analogous to that seen in other branching organs, we also expect similarities of expression regarding those molecules known to be ubiquitous regulators of morphogenesis. In this study, we performed an analysis of the distribution of specific fibroblast growth factors (FGFs), FGF receptors, bone morphogenetic proteins (BMPs) and Pax transcription factors, previously shown to be important for tooth development and/or branching morphogenesis, from the time of initiation of embryonic SMG development until early branching morphogenesis. In addition, we report abnormal SMG phenotypes in FgfR2- IIIc^+/Δ, BMP7^–/–and Pax6^–/– mice. Our results, in comparison with functional studies in other systems, suggest that FGF-2/FGFR-1, FGF-8/FGFR-2(IIIc) and FGF-10/FGFR-2(IIIb) signaling have different paracrine and juxtacrine functions during SMG initial bud formation and branching. Finally, our observations of abnormal SMGs in BMP7^–/– and Pax6^–/–indicate that both BMP7 and Pax6 play important roles during embryonic SMG branching morphogenesis.

Foregut Mesenchyme Contributes Cells to Islets during Pancreatic Development in a 3-Dimensional Avian Model

“…This would make organogenesis of the pancreas more akin in this respect to that of the kidney, 17 a mesodermal organ, than to other endodermal organs such as the lung or submandibular salivary gland. [35][36][37] Indeed nephrons were thought to be derived by branching of the ureteric duct until the metanephric mesenchyme was characterised appropriately 38 and found to form nephrons by an evolutionarily conserved MET. 17,18 SOX genes, expressed both in the developing pancreas 39 and the developing urogenital system, 40 might be candidate mediators of MET in pancreas.…”

Recombinant EDA or Sonic Hedgehog rescue the branching defect in Ectodysplasin A pathway mutant salivary glands in vitro

“…The developing SMG consists of ectodermally derived epithelial branches enclosed within a capsule of cranial neural crest derived mesenchyme (Jaskoll et al, 2002). The SMG is first visible at embryonic day (E) 11.5 (prebud stage) appearing as a thickening of the oral epithelium next to the tongue.…”

Genetic Regulation of Branching Morphogenesis: Lessons Learned from Loss-of-Function Phenotypes

“…Members of the Pax, Fgf, Egf, and Bmp families are expressed in a spatial and temporal pattern consistent with roles in submandibular development (41). Informative phenotypes arising from mutational inactivation of some of these genes have begun to define their functions.…”

“…The spatial expression of Pax6 is restricted to mesenchyme during the early bud stage. Disorganization of mesenchyme and hypoplasia in Pax6 Ϫ/Ϫ mice indicates that Pax6 controls crucial morphogenetic events at this stage (41). FGFR2IIIc, an FGFRIII splice variant, is hypothesized to bind FGF8, expressed in early epithelial buds and later in both epithelium and mesenchyme.…”