Cloning and expression throughout mouse development of mfat1, a homologue of the Drosophila tumour suppressor gene fat.
We present the entire sequence of the mouse Fat orthologue (mFat1), a protein of 4,588 amino acids with 34 cadherin repeats, 27 potential N-glycosylation sites, five EGF repeats and a laminin A G-motif in its extracellular domain. A single transmembrane region is followed by a cytoplasmic domain containing putative catenin-binding sequences. mFat1 shows high homology to human FAT and lesser homology to Drosophila Fat. The sequence of this giant cadherin suggests that it is unlikely to have a homophilic adhesive function, but may mediate heterophilic adhesion or play a signalling role. Expression analysis shows that the mfat1 gene is expressed early in pre-implantation mouse development, at the compact eight cell stage. Whole-mount and section in situ analyses show that transcripts are widely expressed throughout post-implantation development, most notably in the limb buds, branchial arches, forming somites, and in particular in the proliferating ventricular zones in the brain, being down-regulated as cells cease dividing. RT-PCR detects widespread expression in the adult suggesting a role in proliferation and differentiation of many tissues and cell types.
Cox
B
B
Division of Membrane Biology, National Institute for Medical Research, Mill Hill, London, United Kingdom.
Hadjantonakis
A K
AK
Collins
J E
JE
Magee
A I
AI
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000196:embryology / Q000378:metabolism; D015820:Cadherins / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004330:Drosophila; D047108:Embryonic Development; D005314:Embryonic and Fetal Development; D005260:Female; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011247:Pregnancy; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D015053:Zygote
D015820:Cadherins; D018076:DNA, Complementary; C502403:FAT1 protein, human; D008565:Membrane Proteins; C502406:fat1 protein, mouse