scholarly journals Patterning of the chick forebrain anlage by the prechordal plate

Development ◽  
1997 ◽  
Vol 124 (20) ◽  
pp. 4153-4162 ◽  
Author(s):  
E.M. Pera ◽  
M. Kessel
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Relative Concentration ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Lateral Side ◽  
Expression Domain ◽  
Prechordal Plate ◽  
Chick Forebrain

We analysed the role of the prechordal plate in forebrain development of chick embryos in vivo. After transplantation to uncommitted ectoderm a prechordal plate induces an ectopic, dorsoventrally patterned, forebrain-like vesicle. Grafting laterally under the anterior neural plate causes ventralization of the lateral side of the forebrain, as indicated by a second expression domain of the homeobox gene NKX2.1. Such a lateral ventralization cannot be induced by the secreted factor Sonic Hedgehog alone, as this is only able to distort the ventral forebrain medially. Removal of the prechordal plate does not reduce the rostrocaudal extent of the anterior neural tube, but leads to significant narrowing and cyclopia. Excision of the head process results in the caudal expansion of the NKX2.1 expression in the ventral part of the anterior neural tube, while PAX6 expression in the dorsal part remains unchanged. We suggest that there are three essential steps in early forebrain patterning, which culminate in the ventralization of the forebrain. First, anterior neuralization occurs at the primitive streak stage, when BMP-4-antagonizing factors emanate from the node and spread in a planar fashion to induce anterior neural ectoderm. Second, the anterior translocation of organizer-derived cells shifts the source of neuralizing factors anteriorly, where the relative concentration of BMP-4-antagonists is thus elevated, and the medial part of the prospective forebrain becomes competent to respond to ventralizing factors. Third, the forebrain anlage is ventralized by signals including Sonic Hedgehog, thereby creating a new identity, the prospective hypothalamus, which splits the eye anlage into two lateral domains.

Regulation of the twist target gene tinman by modular cis-regulatory elements during early mesoderm development

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 4971-4982 ◽  
Author(s):  
Z. Yin ◽  
X.L. Xu ◽  
M. Frasch
Keyword(s):  
Homeobox Gene ◽  
Regulatory Elements ◽  
Bhlh Protein ◽  
Expression Domain ◽  
Enhancer Activity ◽  
Enhancer Element ◽  
Mesoderm Development ◽  
Visceral Mesoderm

The Drosophila tinman homeobox gene has a major role in early mesoderm patterning and determines the formation of visceral mesoderm, heart progenitors, specific somatic muscle precursors and glia-like mesodermal cells. These functions of tinman are reflected in its dynamic pattern of expression, which is characterized by initial widespread expression in the trunk mesoderm, then refinement to a broad dorsal mesodermal domain, and finally restricted expression in heart progenitors. Here we show that each of these phases of expression is driven by a discrete enhancer element, the first being active in the early mesoderm, the second in the dorsal mesoderm and the third in cardioblasts. We provide evidence that the early-active enhancer element is a direct target of twist, a gene encoding a basic helix-loop-helix (bHLH) protein, which is necessary for tinman activation. This 180 bp enhancer includes three E-box sequences which bind Twist protein in vitro and are essential for enhancer activity in vivo. Ectodermal misexpression of twist causes ectopic activation of this enhancer in ectodermal cells, indicating that twist is the only mesoderm-specific activator of early tinman expression. We further show that the 180 bp enhancer also includes negatively acting sequences. Binding of Even-skipped to these sequences appears to reduce twist-dependent activation in a periodic fashion, thus producing a striped tinman pattern in the early mesoderm. In addition, these sequences prevent activation of tinman by twist in a defined portion of the head mesoderm that gives rise to hemocytes. We find that this repression requires the function of buttonhead, a head-patterning gene, and that buttonhead is necessary for normal activation of the hematopoietic differentiation gene serpent in the same area. Together, our results show that tinman is controlled by an array of discrete enhancer elements that are activated successively by differential genetic inputs, as well as by closely linked activator and repressor binding sites within an early-acting enhancer, which restrict twist activity to specific areas within the twist expression domain.

scholarly journals Sonic Hedgehog induces proliferation of committed skeletal muscle cells in the chick limb

Development ◽  
1998 ◽  
Vol 125 (3) ◽  
pp. 495-505 ◽  
Author(s):  
D. Duprez ◽  
C. Fournier-Thibault ◽  
N. Le Douarin
Keyword(s):  
Sonic Hedgehog ◽  
Primary Cultures ◽  
Posterior Part ◽  
Precursor Cells ◽  
Limb Bud ◽  
Lateral Part ◽  
Expression Domain ◽  
Muscle Precursor ◽  
Muscle Precursor Cells

Myogenic Regulatory Factors (MRFs) are a family of transcription factors whose expression in a cell reflects the commitment of this cell to a myogenic fate before any cytological sign of muscle differentiation is detectable. Myogenic cells in limb skeletal muscles originate from the lateral half of the somites. Cells that migrate away from the lateral part of the somites to the limb bud do not initially express any member of the MRF family. Expression of MRFs in the muscle precursor cells starts after the migration process is completed. The extracellular signals involved in activating the myogenic programme in muscle precursor cells in the limb in vivo are not known. We wished to investigate whether Sonic Hedgehog (SHH) expressed in the posterior part of the limb bud could be involved in differentiation of the muscle precursor cells in the limb. We found that retrovirally overexpressed SHH in the limb bud induced the extension of the expression domain of the Pax-3 gene, then that of the MyoD gene and finally that of the myosin protein. This led to an hypertrophy of the muscles in vivo. Addition of SHH to primary cultures of myoblasts resulted in an increase in the proportion of myoblasts that incorporate bromodeoxyuridine, resulting in an increase of myotube number. These data show that SHH is able to activate myogenesis in vivo and in vitro in already committed myoblasts and suggest that the stimulation of the myogenic programme by SHH involves activation of cell proliferation.

Sonic hedgehog signaling at gastrula stages specifies ventral telencephalic cells in the chick embryo

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3283-3293 ◽  
Author(s):  
L. Gunhaga ◽  
T.M. Jessell ◽  
T. Edlund
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Hedgehog Signaling ◽  
Early Stage ◽  
Primitive Streak ◽  
Cell Types ◽  
Neural Cells ◽  
Sonic Hedgehog Signaling ◽  
Ventral Telencephalon ◽  
Prechordal Mesoderm

A secreted signaling factor, Sonic hedgehog (Shh), has a crucial role in the generation of ventral cell types along the entire rostrocaudal axis of the neural tube. At caudal levels of the neuraxis, Shh is secreted by the notochord and floor plate during the period that ventral cell fates are specified. At anterior prosencephalic levels that give rise to the telencephalon, however, neither the prechordal mesoderm nor the ventral neural tube expresses Shh at the time that the overt ventral character of the telencephalon becomes evident. Thus, the precise role and timing of Shh signaling relevant to the specification of ventral telencephalic identity remains unclear. By analysing neural cell differentiation in chick neural plate explants we provide evidence that neural cells acquire molecular properties characteristic of the ventral telencephalon in response to Shh signals derived from the anterior primitive streak/Hensen's node region at gastrula stages. Exposure of prospective anterior prosencephalic cells to Shh at this early stage is sufficient to initiate a temporal program of differentiation that parallels that of neurons generated normally in the medial ganglionic eminence subdivision of the ventral telencephalon.

Vitronectin is expressed in the ventral region of the neural tube and promotes the differentiation of motor neurons

Development ◽  
1997 ◽  
Vol 124 (24) ◽  
pp. 5139-5147 ◽  
Author(s):  
J.R. Martinez-Morales ◽  
J.A. Barbas ◽  
E. Marti ◽  
P. Bovolenta ◽  
D. Edgar ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Sonic Hedgehog ◽  
Motor Neurons ◽  
Neural Tube ◽  
Matrix Protein ◽  
Floor Plate ◽  
Extracellular Matrix Protein ◽  
Neuron Differentiation

The extracellular matrix protein vitronectin and its mRNA are present in the embryonic chick notochord, floor plate and in the ventral neural tube at the time position of motor neuron generation. When added to cultures of neural tube explants of developmental stage 9, vitronectin promotes the generation of motor neurons in the absence of either notochord or exogenously added Sonic hedgehog. Conversely, the neutralisation of endogenous vitronectin with antibodies inhibits over 90% motor neuron differentiation in co-cultured neural tube/notochord explants, neural tube explants cultured in the presence of Sonic hedgehog, and in committed (stage 13) neural tube explants. Furthermore, treatment of embryos with anti-vitronectin antibodies results in a substantial and specific reduction in the number of motor neurons generated in vivo. These results demonstrate that vitronectin stimulates the differentiation of motor neurons in vitro and in vivo. Since the treatment of stage 9 neural tube explants with Sonic hedgehog resulted in induction of vitronectin mRNA expression before the expression of floor plate markers, we conclude that vitronectin may act either as a downstream effector in the signalling cascade induced by Sonic hedgehog, or as a synergistic factor that increases Shh-induced motor neuron differentiation.

Rpx: a novel anterior-restricted homeobox gene progressively activated in the prechordal plate, anterior neural plate and Rathke's pouch of the mouse embryo

Development ◽  
1996 ◽  
Vol 122 (1) ◽  
pp. 41-52 ◽  
Author(s):  
E. Hermesz ◽  
S. Mackem ◽  
K.A. Mahon
Keyword(s):  
Homeobox Gene ◽  
Cell Types ◽  
Early Embryo ◽  
Neural Plate ◽  
Specific Cell ◽  
Expression Domain ◽  
Rathke’S Pouch ◽  
Rathke's Pouch ◽  
Prechordal Plate ◽  
Early Expression

We have isolated a new murine homeobox gene, Rpx (for Rathke's pouch homeobox), that is dynamically expressed in the prospective cephalic region of the embryo during gastrulation. Early expression is seen in the anterior midline endoderm and prechordal plate precursor. Expression is subsequently activated in the overlying ectoderm of the cephalic neural plate, suggesting that inductive contact with Rpx-expressing mesendoderm is required for this expression. Subsequently, Rpx expression is extinguished in the mesendoderm while remaining in the prospective prosencephalic region of the neural plate ectoderm. Ultimately, transcripts become restricted to Rathke's pouch, the primordium of the pituitary, which is known to be derived from the most anterior ectoderm of the early embryo. Down regulation of Rpx in the pouch coincides with the differentiation of pituitary-specific cell types. Rpx is the earliest known marker for the pituitary primordium, suggestive of a role in the early determination or differentiation of the pituitary. Since Rpx is expressed so dynamically and so early in the anterior region of the embryo, and since its early expression domain is much more extensive than the region fated to form the pituitary, it is likely that Rpx is involved in the initial determination of the anterior (prechordal) region of the embryo.

Anti-apoptotic role of Sonic hedgehog protein at the early stages of nervous system organogenesis

Development ◽  
2001 ◽  
Vol 128 (20) ◽  
pp. 4011-4020 ◽  
Author(s):  
Jean-Baptiste Charrier ◽  
Françoise Lapointe ◽  
Nicole M. Le Douarin ◽  
Marie-Aimée Teillet
Keyword(s):  
Cell Death ◽  
Nervous System ◽  
Chick Embryo ◽  
Sonic Hedgehog ◽  
Neural Tube ◽  
Primitive Streak ◽  
Embryo Cell ◽  
Floor Plate ◽  
Cell Death Program ◽  
Midline Cells

In vertebrates the neural tube, like most of the embryonic organs, shows discreet areas of programmed cell death at several stages during development. In the chick embryo, cell death is dramatically increased in the developing nervous system and other tissues when the midline cells, notochord and floor plate, are prevented from forming by excision of the axial-paraxial hinge (APH), i.e. caudal Hensen’s node and rostral primitive streak, at the 6-somite stage (Charrier, J. B., Teillet, M.-A., Lapointe, F. and Le Douarin, N. M. (1999). Development126, 4771-4783). In this paper we demonstrate that one day after APH excision, when dramatic apoptosis is already present in the neural tube, the latter can be rescued from death by grafting a notochord or a floor plate fragment in its vicinity. The neural tube can also be recovered by transplanting it into a stage-matched chick embryo having one of these structures. In addition, cells engineered to produce Sonic hedgehog protein (SHH) can mimic the effect of the notochord and floor plate cells in in situ grafts and transplantation experiments. SHH can thus counteract a built-in cell death program and thereby contribute to organ morphogenesis, in particular in the central nervous system.

scholarly journals Noggin acts downstream of Wnt and Sonic Hedgehog to antagonize BMP4 in avian somite patterning

Development ◽  
1997 ◽  
Vol 124 (22) ◽  
pp. 4605-4614 ◽  
Author(s):  
E. Hirsinger ◽  
D. Duprez ◽  
C. Jouve ◽  
P. Malapert ◽  
J. Cooke ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Neural Tube ◽  
Body Wall ◽  
Ectopic Expression ◽  
Lateral Compartment ◽  
Lateral Plate ◽  
Vertebrate Embryo ◽  
Myogenic Program ◽  
Epaxial Muscle

In the vertebrate embryo, the lateral compartment of the somite gives rise to muscles of the limb and body wall and is patterned in response to lateral-plate-derived BMP4. Activation of the myogenic program distinctive to the medial somite, i.e. relatively immediate development of the epaxial muscle lineage, requires neutralization of this lateral signal. We have analyzed the properties of molecules likely to play a role in opposing lateral somite specification by BMP4. We propose that the BMP4 antagonist Noggin plays an important role in promoting medial somite patterning in vivo. We demonstrate that Noggin expression in the somite is under the control of a neural-tube-derived factor, whose effect can be mimicked experimentally by Wnt1. Wnt1 is appropriately expressed in the neural tube. Furthermore, we show that Sonic Hedgehog is able to activate ectopic expression of Noggin resulting in the blocking of BMP4 specification of the lateral somite. Our results are consistent with a model in which Noggin activation lies downstream of the SHH and Wnt signaling pathways.

scholarly journals Goosecoid and HNF-3beta genetically interact to regulate neural tube patterning during mouse embryogenesis

Development ◽  
1997 ◽  
Vol 124 (14) ◽  
pp. 2843-2854 ◽  
Author(s):  
S. Filosa ◽  
J.A. Rivera-Perez ◽  
A.P. Gomez ◽  
A. Gansmuller ◽  
H. Sasaki ◽  
...  
Keyword(s):  
Neural Tube ◽  
Double Mutant ◽  
Homeobox Gene ◽  
Primitive Streak ◽  
Signalling Molecules ◽  
Growth Defects ◽  
Fibroblast Growth Factor 8 ◽  
Ventral Neural Tube ◽  
Branchial Arches ◽  
Optic Vesicles

The homeobox gene goosecoid (gsc) and the winged-helix gene Hepatic Nuclear Factor-3beta (HNF-3beta) are co-expressed in all three germ layers in the anterior primitive streak and at the rostral end of mouse embryos during gastrulation. In this paper, we have tested the possibility of functional synergism or redundancy between these two genes during embryogenesis by generating double-mutant mice for gsc and HNF-3beta. Double-mutant embryos of genotype gsc(−/−);HNF-3beta(+/−) show a new phenotype as early as embryonic days 8.75. Loss of Sonic hedgehog (Shh) and HNF-3beta expression was observed in the notochord and ventral neural tube of these embryos. These results indicate that gsc and HNF-3beta interact to regulate Shh expression and consequently dorsal-ventral patterning in the neural tube. In the forebrain of the mutant embryos, severe growth defects and absence of optic vesicles could involve loss of expression of fibroblast growth factor-8, in addition to Shh. Our results also suggest that interaction between gsc and HNF-3beta regulates other signalling molecules required for proper development of the foregut, branchial arches and heart.

scholarly journals Phenotypic Characterization of the Murine Nkx2.6 Homeobox Gene by Gene Targeting

2000 ◽  
Vol 20 (8) ◽  
pp. 2874-2879 ◽  
Author(s):  
Makoto Tanaka ◽  
Naohito Yamasaki ◽  
Seigo Izumo
Keyword(s):  
Thyroid Gland ◽  
Gene Family ◽  
Gene Targeting ◽  
Homeobox Gene ◽  
Phenotypic Characterization ◽  
Lateral Side ◽  
Pharyngeal Pouch ◽  
Short Segment

ABSTRACT The NK-2 homeobox genes have been shown to play critical roles in the development of specific organs and tissues. Nkx2.6 is a member of the NK-2 homeobox gene family and is most closely related to theDrosophila tinman gene. Nkx2.6 is expressed in the caudal pharyngeal pouches, the caudal heart progenitors, the sinus venosus, and the outflow tract of the heart and in a short segment of the gut at early stages of embryogenesis. To investigate the function of Nkx2.6 in vivo, we generated mice with null mutations of Nkx2.6 by the gene targeting technique. Homozygous Nkx2.6 mutant mice were viable and fertile. There were no obvious abnormalities in the caudal pharyngeal pouch derivatives (the thymus, parathyroid glands, and thyroid gland), heart, and gut. Expression of Nkx2.6 overlaps that of Nkx2.5 in the pharynx and heart and that of Nkx2.3 in the pharynx. Interestingly, in mutant embryos homozygous for Nkx2.6, Nkx2.5 expression extended to the lateral side of the pharynx, suggesting a compensatory function of Nkx2.5 in the mutant pharyngeal pouches.

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