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A Hemmati-Brivanlou

Publications and source records attributed to A Hemmati-Brivanlou.

8 recordsLinked to original sources

A truncated activin receptor inhibits mesoderm induction and formation of axial structures in Xenopus embryos.

Activins can induce mesoderm in embryonic explants and have been proposed as the natural inducer in Xenopus. A mutant activin receptor that inhibits activin signalling is used to show that activin is required for the induction of mesoderm in vivo and the patterning of the embryonic body plan. Blocking the activin signal transduction pathway also reveals autonomous induction of a neural marker and unmasks a relationship between activin and fibroblast growth factor.

Activin Receptors

Embryonic expression and functional analysis of a Xenopus activin receptor.

We report the isolation and characterization of a Xenopus activin receptor (XAR1). The amino acid sequence of this protein shows extensive homology with a murine activin receptor. The mRNA is expressed maternally and is ubiquitously distributed during the early stages of embryogenesis. Consistent with a possible role in mesoderm induction and patterning, interference with the normal expression of the receptor by overexpression in the early embryo results in the formation of ectopic dorsal axial structures. During neurulation the XAR1 mRNA is expressed predominantly in the presumptive brain and spinal cord, suggesting an additional function for XAR1 in neurogenesis.

Activin Receptors

A protein expressed in the growth cones of embryonic vertebrate neurons defines a new class of intermediate filament protein.

We have isolated and characterized cDNAs that encode a protein expressed in the axons and growth cones of a subset of Xenopus embryonic neurons. The protein is also expressed in a subset of cells of the brain, including cells in even-numbered rhombomeres, the eye, and the heart. The sequence of the cDNA suggests that the protein belongs to a new class of neural-specific intermediate filaments. Both the RNA and the protein are expressed in the neurula and persist during embryogenesis in the brain, cranial nerves, and spinal cord. Because of the predicted structure of the protein, we have named it tanabin (from the Persian word for rope).

Amino Acid Sequence

Ventral ectoderm of Xenopus forms neural tissue, including hindbrain, in response to activin.

The peptide growth factor Activin A has been shown to induce complete axial structures in explanted blastula animal caps. However, it is not understood how much this response to activin depends upon early signals that prepattern the ectoderm. We have therefore asked what tissues can be induced in blastula animal caps by activin in the absence of early dorsal signals. Using whole-mount in situ hybridization, we compare the expression of three neural markers, N-CAM, En-2 and Krox-20 in activin-treated ectoderm from control and ventralized embryos. In response to activin, both normal and ventralized animal caps frequently form neural tissue (and express N-CAM) and express the hindbrain marker Krox-20. However, the more anterior marker, En-2, is expressed in only a small fraction of normal animal caps and rarely in ventralized animal caps; the frequency of expression does not increase with higher doses of activin. In all cases En-2 and Krox-20 are expressed in coherent patches or stripes in the induced caps. Although mesoderm is induced in both control and ventralized animal caps, notochord is found in response to activin at moderate frequency in control caps, but rarely in ventralized animal caps. These results support the idea that in the absence of other signals, activin treatment elicits hindbrain but not notochord or anterior neural tissue; and thus, the anterior and dorsal extent of tissues formed in response to activin depends on a prior prepatterning or previous inductions.

Activins

Cephalic expression and molecular characterization of Xenopus En-2.

We have isolated and characterized cDNAs corresponding to the Xenopus En-2 gene. Comparison of amino acid sequences between the entire Xenopus En-2 and the Drosophila engrailed proteins confirms conservation of sequences inside as well as proximal to the homeobox and reveals a region of similarity towards the N terminus. Two transcripts encode the Xenopus En-2 protein. Both transcripts are regulated temporally in an identical fashion and are likely to be transcribed from two copies of the En-2 gene. We have also analyzed the distribution of the protein in the head tissue and in the dissected brain of tailbud stage embryos. In addition to the main band of expression at the midbrain-hindbrain boundary, we show that the protein is expressed in three novel areas: the mandibular arch, the optic tectum and the region of anterior pituitary.

Amino Acid Sequence

Region-specific neural induction of an engrailed protein by anterior notochord in Xenopus.

Anterior-specific neural induction can be assayed by means of an antibody that recognizes the Xenopus homeobox-containing protein En-2. The En-2 antigen is an excellent early marker, since it is present as a discrete band in the anterior neural plate of neurula embryos. Regional induction was assayed by combining dorsal mesoderm with competent ectoderm. Anterior notochord from the early neurula induced En-2 frequently, while posterior notochord induced En-2 less frequently. Presumptive somitic mesoderm and presumptive head mesoderm, though they induced neural tissue, were not strong inducers of En-2. Thus, anterior notochord may be the primary mesodermal tissue responsible for the patterning of the anterior neural plate.

Animals

Localization of specific mRNAs in Xenopus embryos by whole-mount in situ hybridization.

We have adapted a non-radioactive technique to detect localized mRNAs in whole-mount Xenopus embryos. Synthetic antisense RNA transcribed in the presence of digoxygenin-UTP is used as a probe and is detected via an anti-digoxygenin antibody. We show that localized mRNAs can be detected from late gastrula to tadpole stages and that high as well as low abundance RNAs can be detected. The method was tested on muscle actin and alpha-globin RNAs, whose localization has previously been characterized. In addition, we used the method to determine the distribution of XA-1 RNA, an anterior ectoderm-specific RNA, which we show is expressed in the periphery of the cement gland as well as in the region of the hatching gland. The sequence of an XA-1 cDNA predicts a protein rich in proline and histidine.

Alpha-Globulins