TGF-β Family Signaling in Early Vertebrate Development

Abstract

TGF-β family ligands function in inducing and patterning many tissues of the early vertebrate embryonic body plan. Nodal signaling is essential for the specification of mesendodermal tissues and the concurrent cellular movements of gastrulation. Bone morphogenetic protein (BMP) signaling patterns tissues along the dorsal-ventral axis and simultaneously directs the cell movements of convergence and extension. After gastrulation, a second wave of Nodal signaling breaks the symmetry between the left and right sides of the embryo. During these processes, elaborate regulatory feedback between TGF-β ligands and their antagonists direct the proper specification and patterning of embryonic tissues. In this review, we summarize the current knowledge of the function and regulation of TGF-β family signaling in these processes. Although we cover principles that are involved in the development of all vertebrate embryos, we focus specifically on three popular model organisms: the mouse , the African clawed frog of the genus, and the zebrafish , highlighting the similarities and differences between these species.

Morphogen dynamics control patterning in a stem cell model of the human embryo

“…Nodal and BMP4 are morphogens crucial for gastrulation in vertebrates 13 . Each pathway has distinct receptor complexes that phosphorylate specific signal transducers, known as receptor-Smads, which then complex with the shared cofactor Smad4 to activate target genes 14 . Here we show in human embryonic stem cells (hESCs) that the response to BMP4 signaling indeed is determined by the ligand concentration, but that unexpectedly, the expression of many mesodermal targets of Activin/Nodal depends on rate of concentration increase.…”

Integrative and perturbation-based analysis of the transcriptional dynamics of TGFβ/BMP system components in transition from embryonic stem cells to neural progenitors

“…[10][11][12][13] The controls involve transcriptional autoregulation and synexpression, as well as feed-forward or feedback mechanisms, acting on the transcription of the signaling system components. [14][15][16][17][18][19] Altogether, this mounts the appropriate transcriptional response in target cells, [20][21][22] which is crucial for embryogenesis, tissue/organ formation and, in the adult, repair after injury. [23][24][25][26][27] Despite significant efforts in identifying and experimentally addressing these regulatory mechanisms, an integrated understanding of the transcriptional dynamics of the TGFβ-family system, and their gene-gene interactions, as a whole is not readily available.…”

Evolution of nodal and nodal‐related genes and the putative composition of the heterodimers that trigger the nodal pathway in vertebrates

“…It is a single‐copy gene in most animal groups, but in vertebrates, it has a paralog called Nodal‐related. The Nodal pathway is active during the pregastrulation and gastrulation stages of development (Shen, ; Zinski, Tajer, & Mullins, ) and is responsible for multiple fundamental processes such as mesoderm induction and patterning, endoderm function, neural patterning, establishment of left‐right asymmetry, dorsal‐ventral axis specification, anterior–posterior axis formation, and maintenance of undifferentiated embryonic stem cells (Conlon, Lyons, Takaesu, Barth, & Kispert, ; Feldman et al, ; Jones et al, ; Schier, ; Shen, ). Recently, three independent groups have shown that in vertebrates Nodal needs to form heterodimers with the GDF1/3 protein, encoded by another member of the TGF‐β superfamily, to activate the signaling pathway (Bisgrove, Su, & Yost, ; Montague & Schier, ; Pelliccia, Jindal, & Burdine, ).…”