Sharp developmental thresholds defined through bistability by antagonistic gradients of retinoic acid and FGF signaling.
نویسندگان
چکیده
The establishment of thresholds along morphogen gradients in the embryo is poorly understood. Using mathematical modeling, we show that mutually inhibitory gradients can generate and position sharp morphogen thresholds in the embryonic space. Taking vertebrate segmentation as a paradigm, we demonstrate that the antagonistic gradients of retinoic acid (RA) and Fibroblast Growth Factor (FGF) along the presomitic mesoderm (PSM) may lead to the coexistence of two stable steady states. Here, we propose that this bistability is associated with abrupt switches in the levels of FGF and RA signaling, which permit the synchronized activation of segmentation genes, such as mesp2, in successive cohorts of PSM cells in response to the segmentation clock, thereby defining the future segments. Bistability resulting from mutual inhibition of RA and FGF provides a molecular mechanism for the all-or-none transitions assumed in the "clock and wavefront" somitogenesis model. Given that mutually antagonistic signaling gradients are common in development, such bistable switches could represent an important principle underlying embryonic patterning.
منابع مشابه
All-trans Retinoic Acid Regulates the Balance of Treg-Th17 Cells through ERK and P38 Signaling Pathway
متن کامل
FGF and retinoic acid activity gradients control the timing of neural crest cell emigration in the trunk
Coordination between functionally related adjacent tissues is essential during development. For example, formation of trunk neural crest cells (NCCs) is highly influenced by the adjacent mesoderm, but the molecular mechanism involved is not well understood. As part of this mechanism, fibroblast growth factor (FGF) and retinoic acid (RA) mesodermal gradients control the onset of neurogenesis in ...
متن کامل9-cis-Retinoic Acid and 1,25-dihydroxy Vitamin D3 Improve the Differentiation of Neural Stem Cells into Oligodendrocytes through the Inhibition of the Notch and Wnt Signaling Pathways
Background: Differentiating oligodendrocyte precursor cells (OPCs) into oligodendrocytes could be improved by inhibiting signaling pathways such as Wnt and Notch. 9-cis-retinoic acid (9-cis-RA) and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) can ameliorate oligodendrogenesis. We investigated whether they could increase oligodendrogenesis by inhibiting the Wnt and Notch signaling pathways.Methods: Co...
متن کاملThe road to the vertebral formula.
In vertebrates, the paraxial mesoderm differentiates into several structures, including the axial skeleton. The genetic mechanisms that control positional information in the paraxial mesoderm along the anterior-posterior axis are responsible for the development of a skeleton with the appropriate vertebral formula, i.e. a specific number of cervical, thoracic, lumbar, sacral and caudal vertebrae...
متن کاملAnalysis of Promyelocytic Leukemia in Human Embryonic Carcinoma Stem Cells During Retinoic Acid-Induced Neural Differentiation
Background: Promyelocytic leukemia protein (PML) is a tumor suppressor protein that is involved in myeloid cell differentiation in response to retinoic acid (RA). In addition, RA acts as a natural morphogen in neural development. Objectives: This study aimed to examine PML gene expression in different stages of in vitro neural differentiation of NT2 cells, and to investigate the possible role o...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Developmental dynamics : an official publication of the American Association of Anatomists
دوره 236 6 شماره
صفحات -
تاریخ انتشار 2007