Disruption of somitogenesis by a novel dominant allele of Lfng suggests important roles for protein processing and secretion.

Vertebrate somitogenesis is regulated by a segmentation clock. Clock-linked genes exhibit cyclic expression, with a periodicity matching the rate of somite production. In mice, lunatic fringe (Lfng) expression oscillates, and LFNG protein contributes to periodic repression of Notch signaling.

Identification of genes expressed in the migrating primitive myeloid lineage of Xenopus laevis.

Background: During primitive hematopoiesis in Xenopus, cebpa and spib expressing myeloid cells emerge from the anterior ventral blood island. Primitive myeloid cells migrate throughout the embryo and are critical for immunity, healing, and development. Although definitive hematopoiesis has been studied extensively, molecular mechanisms leading to the migration of primitive myelocytes remain poorly understood.

A Molecular atlas of Xenopus respiratory system development.

Background: Respiratory system development is regulated by a complex series of endoderm-mesoderm interactions that are not fully understood. Recently Xenopus has emerged as an alternative model to investigate early respiratory system development, but the extent to which the morphogenesis and molecular pathways involved are conserved between Xenopus and mammals has not been systematically documented.

Results: In this study, we provide a histological and molecular atlas of Xenopus respiratory system development, focusing on Nkx2.

Posterior skeletal development and the segmentation clock period are sensitive to Lfng dosage during somitogenesis.

The segmental structure of the axial skeleton is formed during somitogenesis. During this process, paired somites bud from the presomitic mesoderm (PSM), in a process regulated by a genetic clock called the segmentation clock. The Notch pathway and the Notch modulator Lunatic fringe (Lfng) play multiple roles during segmentation.

Prolonged FGF signaling is necessary for lung and liver induction in Xenopus.

Background: FGF signaling plays numerous roles during organogenesis of the embryonic gut tube. Mouse explant studies suggest that different thresholds of FGF signaling from the cardiogenic mesoderm induce lung, liver, and pancreas lineages from the ventral foregut progenitor cells. The mechanisms that regulate FGF dose in vivo are unknown.

Sizzled-tolloid interactions maintain foregut progenitors by regulating fibronectin-dependent BMP signaling.

The liver, pancreas, and lungs are induced from endoderm progenitors by a series of dynamic growth factor signals from the mesoderm, but how the temporal-spatial activity of these signals is controlled is poorly understood. We have identified an extracellular regulatory loop required for robust bone morphogenetic protein (BMP) signaling in the Xenopus foregut. We show that BMP signaling is required to maintain foregut progenitors and induce expression of the secreted frizzled related protein Sizzled (Szl) and the extracellular metalloprotease Tolloid-like 1 (Tll1).

Manic fringe is not required for embryonic development, and fringe family members do not exhibit redundant functions in the axial skeleton, limb, or hindbrain.

Tight regulation of Notch pathway signaling is important in many aspects of embryonic development. Notch signaling can be modulated by expression of fringe genes, encoding glycosyltransferases that modify EGF repeats in the Notch receptor. Although Lunatic fringe (Lfng) has been shown to play important roles in vertebrate segmentation, comparatively little is known regarding the developmental functions of the other vertebrate fringe genes, Radical fringe (Rfng) and Manic fringe (Mfng).

Lunatic fringe protein processing by proprotein convertases may contribute to the short protein half-life in the segmentation clock.

During vertebrate segmentation, oscillatory activation of Notch signaling is important in the clock that regulates the timing of somitogenesis. In mice, the cyclic activation of NOTCH1 requires the periodic expression of Lunatic fringe (Lfng). For LFNG to play a role in the segmentation clock, its cyclic transcription must be coupled with post-translational mechanisms that confer a short protein half-life.

Oscillatory lunatic fringe activity is crucial for segmentation of the anterior but not posterior skeleton.

The Notch pathway plays multiple roles during vertebrate somitogenesis, functioning in the segmentation clock and during rostral/caudal (R/C) somite patterning. Lunatic fringe (Lfng) encodes a glycosyltransferase that modulates Notch signaling, and its expression patterns suggest roles in both of these processes. To dissect the roles played by Lfng during somitogenesis, a novel allele was established that lacks cyclic Lfng expression within the segmentation clock, but that maintains expression during R/C somite patterning (Lfng(DeltaFCE1)).

The vertebrate segmentation clock and its role in skeletal birth defects.

The segmental structure of the vertebrate body plan is most evident in the axial skeleton. The regulated generation of somites, a process called somitogenesis, underlies the vertebrate body plan and is crucial for proper skeletal development. A genetic clock regulates this process, controlling the timing of somite development.