Anti-neural-inhibition: a conserved mechanism for neural induction.
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FGF receptor signalling is required to maintain neural progenitors during Hensen's node progression.
Previous analyses of labelled clones of cells within the developing nervous system of the mouse have indicated that descendants are initially dispersed rostrocaudally followed by more local proliferation, which is consistent with the progressing node's contributing descendants from a resident population of progenitor cells as it advances caudally. Here we electroporated an expression vector encoding green fluorescent protein into the chicken embryo near Hensen's node to test and confirm the pattern inferred in the mouse. This provides a model in which a proliferative stem zone is maintained in the node by a localized signal; those cells that are displaced out of the stem zone go on to contribute to the growing axis. To test whether fibroblast growth factor (FGF) signalling could be involved in the maintenance of the stem zone, we co-electroporated a dominant-negative FGF receptor with a lineage marker, and found that it markedly alters the elongation of the spinal cord primordium. The results indicate that FGF receptor signalling promotes the continuous development of the posterior nervous system by maintaining presumptive neural progenitors in the region near Hensen's node. This offers a potential explanation for the mixed findings on FGF in the growth and patterning of the embryonic axis.
Animals↗
Neural induction.
The molecular mechanism of neural induction of embryonic cells is an important but poorly understood problem in neuroembryology. Glycoconjugates in the target cell plasma membrane and/or its structural organization play a key role in the reception of the inductive signal. It is the competent target tissue itself which probably contains the capacity and specificity for neuralization. However, the mechanism of transmission of the signal which leads to activation of the intracellular machinery involved in the process of neural determination remains to be elucidated. With respect to the information acquired by the target cells during neural induction, and the early events in differentiation, neuronal precursor cells have been shown to have acquired the potential to display a high degree of biochemical and phenotypic differentiation, even in the absence of further embryonic influences.
Animals↗
Induction of yolk sac endoderm in GATA-4-deficient embryoid bodies by retinoic acid.
GATA-4, a transcription factor implicated in lineage determination, is expressed in both parietal and visceral endoderm of the early mouse embryo. In embryonic stem cell-derived embryoid bodies, GATA-4 mRNA is first detectable at 4-5 days of differentiation and is confined to visceral endoderm cells on the surface of the bodies. Previously we reported that targeted mutagenesis of the Gata4 gene in embryonic stem cells results in a block in visceral endoderm differentiation in vitro. In an attempt to elucidate the role of GATA-4 in the formation of visceral endoderm, we have now differentiated Gata4 -/- and wild type embryoid bodies in the presence of retinoic acid +/- dbcAMP, known inducers of endoderm formation. We show that differentiation of Gata4 -/- embryoid bodies in the presence of retinoic acid results in formation of visceral endoderm, while differentiation of Gata4 -/- embryoid bodies in the presence of retinoic acid plus dbcAMP causes parietal endoderm formation. The presence of these yolk sac endoderm layers was confirmed by light microscopy and analysis of biochemical markers including alpha-fetoprotein, type IV collagen, laminin, and binding sites for Dolichos biflorus agglutinin. Treatment of Gata4 -/- embryoid bodies with retinoic acid induces expression of another GATA-binding protein, GATA-6, in both visceral and parietal endoderm cells. That another GATA-binding protein is induced in the absence of GATA-4 suggests that this family of transcription factors plays an important role in yolk sac differentiation.
Animals↗
Induction and specification of cranial placodes.
Cranial placodes are specialized regions of the ectoderm, which give rise to various sensory ganglia and contribute to the pituitary gland and sensory organs of the vertebrate head. They include the adenohypophyseal, olfactory, lens, trigeminal, and profundal placodes, a series of epibranchial placodes, an otic placode, and a series of lateral line placodes. After a long period of neglect, recent years have seen a resurgence of interest in placode induction and specification. There is increasing evidence that all placodes despite their different developmental fates originate from a common panplacodal primordium around the neural plate. This common primordium is defined by the expression of transcription factors of the Six1/2, Six4/5, and Eya families, which later continue to be expressed in all placodes and appear to promote generic placodal properties such as proliferation, the capacity for morphogenetic movements, and neuronal differentiation. A large number of other transcription factors are expressed in subdomains of the panplacodal primordium and appear to contribute to the specification of particular subsets of placodes. This review first provides a brief overview of different cranial placodes and then synthesizes evidence for the common origin of all placodes from a panplacodal primordium. The role of various transcription factors for the development of the different placodes is addressed next, and it is discussed how individual placodes may be specified and compartmentalized within the panplacodal primordium. Finally, tissues and signals involved in placode induction are summarized with a special focus on induction of the panplacodal primordium itself (generic placode induction) and its relation to neural induction and neural crest induction. Integrating current data, new models of generic placode induction and of combinatorial placode specification are presented.
Animals↗
Sclerotome induction and differentiation.
Inductive events in the development of the sclerotome and their possible underlying mechanisms were reviewed from the primary literature. A brief review of morphological and anatomical aspects of sclerotome development was given. The importance of the notochord and neural tube in sclerotome induction and somite chondrogenesis in vivo and in vitro was established. The functions and patterns of expression of different sclerotome markers were discussed. Shh and Noggin were discussed as two molecules produced by the neural tube and notochord that appear to maintain and initiate the sclerotome, respectively. While the abilities of the axial organs and Shh and Noggin to induce sclerotome marker expression in the somite was not disputed, the exact nature of these inductions was discussed with regard to possible effects on gene expression, effects on cell survival, and physical effects on the cells and it was argued that the fundamental nature of inductive events in the sclerotome is still unknown.
Animals↗
Progress in studies on the induction and differentiation of embryonic stem cells.
Embryonic stem cells (ESCs), which are isolated from the inner cell mass of the blastocyst stage embryo, have the potential to give rise to an entire organism and to generate every body cell type. Much improvement has been made in the field of induction and differentiation of ESCs during the last two years, such as the ESCs differentiation into germ cells (2003) and the cloning of human ESCs (2004), both of which were chosen respectively as one of the top ten achievements evaluated by academic journals. Great attention was also paid to the research of the new genes which could maintain ESCs in the undifferentiated state and the research of the induction and differentiation of ESCs.
Animals↗
Endogenous and ectopic gland induction by FGF-10.
FGF-10, a member of the fibroblast growth factor family, is expressed in mesodermally derived cell populations during embryogenesis. During normal ocular development, FGF-10 is expressed in the perioptic mesenchyme adjacent to the Harderian and lacrimal gland primordia. In this report, we provide evidence that FGF-10 is both necessary and sufficient to initiate glandular morphogenesis. Lens-specific expression of FGF-10 was sufficient to induce ectopic ocular glands within the cornea. In addition, lacrimal and Harderian glands were not seen in FGF-10 null fetuses. Based on these results we propose that FGF-10 is an inductive signal that initiates ocular gland morphogenesis.
Animals↗
Chemokines in lymphopoiesis and lymphoid organ development.
An important role has emerged for chemokines in regulating the distribution of progenitor cells during hematopoietic cell development. As well as recruiting cells, chemokines promote cell retention and cytokine expression. Furthermore, chemokines have been found to have an inductive function in secondary lymphoid organ development.
Animals↗
[Lack of negative regulation of beta-adrenoreceptor affinity by guanine nucleotides in embryonic membranes and its induction by the GTP-binding protein from mature protein].
The negative regulation of the beta-adrenoreceptor affinity by guanine nucleotides in the sarcolemmal fraction of chicken skeletal muscle at different stages of ontogenesis was studied. It was found that the negative regulation is absent in the embryonic period; the effect of GTP is manifested only before hatching, whereas that of Gpp(NH)p--at later periods, i.e., in 1-month-old chickens. Similar age-dependent dynamics was revealed with respect to the GTP effect on the dissociation rate of the [3H]DHA-beta-adrenoreceptor complex. An addition to the system containing embryonic muscle membranes of the GTP-binding protein isolated from skeletal muscle and liver of chickens whose age exceeds 20 days led to earlier manifestations of the above effects (on the 13th-15th embryonic days). The data obtained testify to the limiting role of GTP-binding proteins in the negative control of the hormone-receptor interaction and support the authors' hypothesis on the absence in the embryonic muscle of the 42 kD GTP-binding protein responsible for the functional coupling of the hormone-sensitive adenylate cyclase components.
Aging↗
Biological significance of dermal Merkel cells in development of cutaneous nerves in human fetal skin.
We detected epidermal Merkel cells in 12-week fetuses with monoclonal antibodies (MAb) against simple epithelium keratin and epithelial membrane antigen. In 15-week fetuses these Merkel cells began to descend into the dermis and expressed nerve growth factor receptors (NGF-R). At approximately the same time, cutaneous nerves, as detected with an MAb against neurofilaments, extended from the subcutaneous trunk and branched to form the subepidermal nerve plexus. The expression of NGF-R on dermal Merkel cells preceded their connection with immunoreactive small nerves. Initially, most of these fine nerve endings were directed towards dermal Merkel cells. In 23-week fetuses the subepidermal nerve plexus was well developed and immunoreactive dermal Merkel cells began to disappear. At all stage of fetal development the epidermal Merkel cells did not strongly express NGF-R. We postulate that dermal Merkel cells play an inductive and a promotional role in development of the cutaneous nerve plexus in the upper dermis.
Embryonic Induction↗
Strategies for the generation of neuronal diversity in the developing central nervous system.
During development, the neural tube produces a large diversity of neuronal phenotypes from a morphologically homogeneous pool of precursor cells. In recent years, the cellular and molecular mechanisms by which specific types of neurons are generated have been explored, in the hope of discovering features common to development throughout the nervous system. This article focuses on three strategies employed by the CNS to generate distinct classes of neuronal phenotypes during development: dorsal-ventral polarization in the spinal cord, segmentation in the hindbrain, and a lamination in the cerebral cortex. The mechanisms for neurogenesis exemplified by these three strategies range from a relatively rigid, cell lineage-dependent specification with a high degree of subservance to early patterns of gene expression, to inductions and cell-cell interactions that determine cell fates more flexibly.
Animals↗
Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice.
Lymphoid enhancer factor 1 (LEF-1) is a sequence-specific DNA-binding protein that is expressed in pre-B and T lymphocytes of adult mice, and in the neural crest, mesencephalon, tooth germs, whisker follicles, and other sites during embryogenesis. We have generated mice carrying a homozygous germ-line mutation in the LEF-1 gene that eliminates its protein expression and causes postnatal lethality. The mutant mice lack teeth, mammary glands, whiskers, and hair but show no obvious defects in lymphoid cell populations at birth. The LEF-1-deficient mice also lack the mesencephalic nucleus of the trigeminal nerve, the only neural crest-derived neuronal populations. Together, the pattern of these defects suggest an essential role for LEF-1 in the formation of several organs and structures that require inductive tissue interactions.
Animals↗
The TGF-beta-related DVR gene family in mammalian development.
The genes that encode the bone morphogenetic proteins and the Vg-related proteins are mammalian members of a group of TGF-beta-related genes, designated the DVR family, that includes the decapentaplegic gene of Drosophila and the Vg1 gene of Xenopus. Members of the DVR (decapentaplegic-Vg-related) family have been implicated in diverse processes during development, particularly in epithelial-mesenchymal interactions. The results of our in situ hybridization studies with postimplantation mouse embryos provide evidence for the involvement of DVR family members, particularly DVR-2, DVR-4 and DVR-6, in specific inductive interactions during the development of many organs, including the limb, the whisker follicle and the heart.
Animals↗
Dorso-ventral limb polarity and origin of the ridge: on the fringe of independence?
Molecular and developmental studies of limb pattern formation have recently gained widespread attention. The fact that vertebrate limbs are amenable to both genetic and embryological manipulations has established this model system as a valuable paradigm for studying vertebrate development. Limb buds are polarised along all three major axes and the establishment of the dorso-ventral (DV) polarity is dependent upon cues localised in the trunk, where a DV ectodermal interface is produced by confrontation of dorsal and ventral identities. By analogy to Drosophila imaginal disc development, this interface has been proposed to determine and position an ectodermal organising centre, the Apical Ectodermal Ridge (AER), controlling limb bud outgrowth. Recent fate mapping studies and studies of genes regulating DV limb polarity, AER formation and differentiation suggest, however, that DV patterning and AER induction, though coordinately regulated during limb bud outgrowth, may early on be more dissociated than expected.
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Grg3, a murine Groucho-related gene, is expressed in the developing nervous system and in mesenchyme-induced epithelial structures.
We have isolated cDNAs representing multiple members of murine groucho homologues, designated Grg for groucho-related genes. Among them, Grg3 appears to produce two transcripts. One of the Grg3 transcripts contains coding sequence for a complete Groucho protein homologue. The second transcript contains coding sequence for only the two amino-terminal domains of the Groucho protein, followed by a hydrophobic tail and a stop codon. We analyzed the expression of both transcripts in mouse embryos using RNase protection and in situ hybridization. Expression was detected during cell determination in the nervous system and in somitic mesoderm, overlapping Notch1 expression and adjacent to Mash1, MyoD and Myf5 expression. Thus, the expression pattern of Grg3 suggests a conserved role in the Notch signalling pathway to regulate expression of basic helix-loop-helix proteins and cell determination. Grg3 expression was also consistently detected in epithelial structures undergoing mesenchyme induction.
Alternative Splicing↗
Planar and vertical induction of anteroposterior pattern during the development of the amphibian central nervous system.
In amphibians and other vertebrates, neural development is induced in the ectoderm by signals coming from the dorsal mesoderm during gastrulation. Classical embryological results indicated that these signals follow a "vertical" path, from the involuted dorsal mesoderm to the overlying ectoderm. Recent work with the frog Xenopus laevis, however, has revealed the existence of "planar" neural-inducing signals, which pass within the continuous sheet or plane of tissue formed by the dorsal mesoderm and presumptive neurectoderm. Much of this work has made use of Keller explants, in which dorsal mesoderm and ectoderm are cultured in a planar configuration with contact along only a single edge, and vertical contact is prevented. Planar signals can induce the full anteroposterior (A-P) extent of neural pattern, as evidenced in Keller explants by the expression of genes that mark specific positions along the A-P axis. In this review, classical and modern molecular work on vertical and planar induction will be discussed. This will be followed by a discussion of various models for vertical induction and planar induction. It has been proposed that the A-P pattern in the nervous system is derived from a parallel pattern of inducers in the dorsal mesoderm which is "imprinted" vertically onto the overlying ectoderm. Since it is now known that planar signals can also induce A-P neural pattern, this kind of model must be reassessed. The study of planar induction of A-P pattern in Xenopus embryos provides a simple, manipulable, two-dimensional system in which to investigate pattern formation.
Amphibians↗
Wnt signaling in Xenopus embryos inhibits bmp4 expression and activates neural development.
We report a new role for Wnt signaling in the vertebrate embryo: the induction of neural tissue from ectoderm. Early expression of mouse wnt8, Xwnt8, beta-catenin, or dominant-negative GSK3 induces the expression of neural-specific markers and inhibits the expression of Bmp4 in Xenopus ectoderm. We show that Wnt8, but not the BMP antagonist Noggin, can inhibit Bmp4 expression at early gastrula stages. Furthermore, inhibition of beta-catenin activity in the neural ectoderm of whole embryos by a truncated TCF results in a decrease in neural development. Therefore, we suggest that a cleavage-stage Wnt signal normally contributes to an early repression of Bmp4 on the dorsal side of the embryo and sensitizes the ectoderm to respond to neural inducing signals from the organizer. The Wnt targets Xnr3 and siamois have been shown previously to have neuralizing activity when overexpressed. However, antagonists of Wnt signaling, dnXwnt8 and Nxfrz8, inhibit Wnt-mediated Xnr3 and siamois induction, but not neural induction, suggesting an alternative mechanism for Bmp repression and neuralization. Conversely, dnTCF blocks both Wnt-mediated Xnr3 and neural induction, suggesting that both pathways require this transcription factor.
Animals↗