The objective of this work is to understand early vertebrate development at the molecular level. Approaches include the isolation of genes that play a critical role, analysis of their expression and function, and examination of the mechanisms whereby patterns of gene expression are altered in early development. The amphibian Xenopus has been chosen as the experimental animal because the embryos are large and easy to manipulate surgically, and the function of macromolecules, such as mRNA or protein, can be assayed by injection into living embryos. Furthermore, the early stages of development when the dorso-ventral and antero-posterior axes form are readily accessible to biochemical and embryological analysis. The molecular mechanisms which determine cell fate are conserved among vertebrates, so the findings from this work will further the understanding of development of all vertebrate species, including man. The objectives of this proposal are: 1) to determine the molecular basis for instability of a class of maternal RNAs that include homeobox-containing transcripts; the endonuclease that initiates degradation of the mRNAs will be purified, and its specificity and control elucidated. 2) to determine the mechanisms whereby specific genes are regulated to produce the detailed pattern of the embryo. Molecular markers will be used to determine the molecular basis for induction of different regions of the neural plate by underlying mesoderm and neighboring ectoderm. The role of peptide growth factors in regional induction will be scrutinized. Regional induction of the neural plate depends on prior regionalization of the dorsal mesoderm. To further understand the progressive restriction of mesodermal cell fate, the formation of muscle tissue will be used as a model. Progressive localization of MyoD transcripts and the role of a newly identified gene expressed in myotomes will be explored. A new structural motif in this gene was identified using antibodies to a heterologous protein. The same approach has been used to identify other motifs including a protein expressed on the surface of dorsal gastrula cells. The function of these newly identified proteins will be assayed in the embryo and in cell culture.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM042341-08
Application #
3300823
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1988-09-01
Project End
1995-08-31
Budget Start
1992-09-01
Budget End
1993-08-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Mena, Elijah L; Kjolby, Rachel A S; Saxton, Robert A et al. (2018) Dimerization quality control ensures neuronal development and survival. Science 362:
Willsey, Helen Rankin; Walentek, Peter; Exner, Cameron R T et al. (2018) Katanin-like protein Katnal2 is required for ciliogenesis and brain development in Xenopus embryos. Dev Biol 442:276-287
Sun, Dingyuan I; Tasca, Alexia; Haas, Maximilian et al. (2018) Na+/H+ Exchangers Are Required for the Development and Function of Vertebrate Mucociliary Epithelia. Cells Tissues Organs :1-14
Stafford, David A; Dichmann, Darwin S; Chang, Jessica K et al. (2017) Deletion of the sclerotome-enriched lncRNA PEAT augments ribosomal protein expression. Proc Natl Acad Sci U S A 114:101-106
Kjolby, Rachel A S; Harland, Richard M (2017) Genome-wide identification of Wnt/?-catenin transcriptional targets during Xenopus gastrulation. Dev Biol 426:165-175
Shyer, Amy E; Rodrigues, Alan R; Schroeder, Grant G et al. (2017) Emergent cellular self-organization and mechanosensation initiate follicle pattern in the avian skin. Science 357:811-815
Exner, Cameron R T; Kim, Albert Y; Mardjuki, Sarah M et al. (2017) sall1 and sall4 repress pou5f3 family expression to allow neural patterning, differentiation, and morphogenesis in Xenopus laevis. Dev Biol 425:33-43
Young, John J; Kjolby, Rachel A S; Wu, Gloria et al. (2017) Noggin is required for first pharyngeal arch differentiation in the frog Xenopus tropicalis. Dev Biol 426:245-254
Walentek, Peter; Quigley, Ian K; Sun, Dingyuan I et al. (2016) Ciliary transcription factors and miRNAs precisely regulate Cp110 levels required for ciliary adhesions and ciliogenesis. Elife 5:
Session, Adam M; Uno, Yoshinobu; Kwon, Taejoon et al. (2016) Genome evolution in the allotetraploid frog Xenopus laevis. Nature 538:336-343

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