Protein Has An Evolutionarily-Conserved Function In Gastrulation

Developmental biologist Lewis Wolpert has famously quipped that gastrulation is the most important time of one's life. As a vertebrate embryo develops, it begins as a relatively uniform, undifferentiated ball of cells, and progresses to become a complex, interdependent assembly of cells whose fate is at least partially restricted. Gastrulation, which begins in the mouse embryo on the sixth day of gestation, is the process whereby orchestrated cellular migration establishes the three so-called 'germ layers' of the embryo (ectoderm, mesoderm, endoderm) that eventually give rise to all of the differentiated cell types of the body. Now, Elizabeth Lacy and colleagues (of Memorial Sloan-Kettering Cancer Center, New York) describe the cloning and characterization of a gene, expressed during gastrulation, that was previously shown to be required for the development of the organs of the trunk-limb buds, dermis, muscle, vertebrae and others (Nature Genetics, Vol. 27, Issue 4, 01 April 2001).

The initial production of the 'trunkless' embryo was due to the serendipitous disruption of a region on chromosome 12 by a fragment of DNA that the researchers were using to mutate different regions of the mouse genome. The disrupted gene(s)--called amnionless (amn) because the mutant embryos also lack an amnion--had remained uncharacterized. The authors now show that their DNA insertion eliminated 5 of the 12 exons of a single gene. When the entire amn gene is 'knocked out' by conventional gene-targeting methods, the phenotype of these mutant embryos turns out to be identical to that of the embryos harboring the original insertion on chromosome 12.

What does the amn protein do? The amino acid sequence provides a clue, in that the protein contains a 'cysteine-rich' domain that suggests it might act as a modulator of the activities of the bone morphogenetic proteins (BMPs)--a group of secreted factors that regulate many aspects of embryonic development. Amn is normally expressed during gastrulation in the visceral endoderm, an extra-embryonic tissue that is required for the patterning and development of the embryo proper. The authors propose a model in which amn might regulate the activity of one or more BMPs, thereby affecting the development of the visceral endoderm, which in turn influences the patterning of the overlying embryo. In an accompanying News & Views, Ray Dunn (of Harvard University, Boston, Massachusetts) and Brigid Hogan (of Vanderbilt University, Nashville, Tennessee) provide a helpful picture of the ways in which amn might contribute to early mouse development. As fruit fly and human versions of amn have also been identified, it seems probable that this protein has an evolutionarily-conserved function in gastrulation.

CONTACT:

Dr. Elizabeth Lacy
Memorial Sloan-Kettering Cancer Center
New York, New York, USA
Telephone: +1 (212) 639 7538
Fax: +1 (646) 422 2062
e-mail: e-lacy@ski.mskcc.org

Dr Brigid L. Hogan
Vanderbilt University Medical Center
Nashville, Tennessee, USA
Telephone: +1 (615) 343-6418
Fax: +1 (615) 343-4539
e-mail: brigid.hogan@mcmail.vanderbilt.edu

(C) Nature Genetics press release.

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