Mice Lacking the Giant Protocadherin MFAT1 Exhibit Renal Slit Junction Abnormalities and a Partially Penetrant Cyclopia and Anophthalmia Phenotype

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2003 May 2

PMID 12724416

Citations 89

Authors

Lorenza Ciani

Anjla Patel

Nicholas D Allen

Charles ffrench-Constant

Affiliations

Soon will be listed here.

Abstract

While roles in adhesion and morphogenesis have been documented for classical cadherins, the nonclassical cadherins are much less well understood. Here we have examined the functions of the giant protocadherin FAT by generating a transgenic mouse lacking mFAT1. These mice exhibit perinatal lethality, most probably caused by loss of the renal glomerular slit junctions and fusion of glomerular epithelial cell processes (podocytes). In addition, some mFAT1(-/-) mice show defects in forebrain development (holoprosencephaly) and failure of eye development (anophthalmia). In contrast to Drosophila, where FAT acts as a tumor suppressor gene, we found no evidence for abnormalities of proliferation in two tissues (skin and central nervous system [CNS]) containing stem and precursor cell populations and in which FAT is expressed strongly. Our results confirm a necessary role for FAT1 in the modified adhesion junctions of the renal glomerular epithelial cell and reveal hitherto unsuspected roles for FAT1 in CNS development.

Citing Articles

Characterization of Freshly Isolated Human Peripheral Blood B Cells, Monocytes, CD4+ and CD8+ T Cells, and Skin Mast Cells by Quantitative Transcriptomics.

Akula S, Alvarado-Vazquez A, Haide Mendez Enriquez E, Bal G, Franke K, Wernersson S Int J Mol Sci. 2024; 25(23).

PMID: 39684762 PMC: 11642334. DOI: 10.3390/ijms252313050.

Iterative oxidation by TET1 is required for reprogramming of imprinting control regions and patterning of mouse sperm hypomethylated regions.

Prasasya R, Caldwell B, Liu Z, Wu S, Leu N, Fowler J Dev Cell. 2024; 59(8):1010-1027.e8.

PMID: 38569549 PMC: 11042979. DOI: 10.1016/j.devcel.2024.02.012.

The FAT1 Cadherin Drives Vascular Smooth Muscle Cell Migration.

Riascos-Bernal D, Ressa G, Korrapati A, Sibinga N Cells. 2023; 12(12).

PMID: 37371091 PMC: 10297709. DOI: 10.3390/cells12121621.

FAT1 expression in T-cell acute lymphoblastic leukemia (T-ALL) modulates proliferation and WNT signaling.

Liebig S, Neumann M, Silva P, Ortiz-Tanchez J, Schulze V, Isaakidis K Sci Rep. 2023; 13(1):972.

PMID: 36653435 PMC: 9849452. DOI: 10.1038/s41598-023-27792-0.

Repression and 3D-restructuring resolves regulatory conflicts in evolutionarily rearranged genomes.

Ringel A, Szabo Q, Chiariello A, Chudzik K, Schopflin R, Rothe P Cell. 2022; 185(20):3689-3704.e21.

PMID: 36179666 PMC: 9567273. DOI: 10.1016/j.cell.2022.09.006.

References

Adler R, Belecky-Adams T . The role of bone morphogenetic proteins in the differentiation of the ventral optic cup. Development. 2002; 129(13):3161-71. DOI: 10.1242/dev.129.13.3161. View

Rantanen M, Palmen T, Patari A, Ahola H, Lehtonen S, Astrom E . Nephrin TRAP mice lack slit diaphragms and show fibrotic glomeruli and cystic tubular lesions. J Am Soc Nephrol. 2002; 13(6):1586-94. DOI: 10.1097/01.asn.0000016142.29721.22. View

Mahoney P, Weber U, Onofrechuk P, Biessmann H, Bryant P, Goodman C . The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily. Cell. 1991; 67(5):853-68. DOI: 10.1016/0092-8674(91)90359-7. View

Reynolds B, Weiss S . Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992; 255(5052):1707-10. DOI: 10.1126/science.1553558. View

Saha M, Servetnick M, GRAINGER R . Vertebrate eye development. Curr Opin Genet Dev. 1992; 2(4):582-8. DOI: 10.1016/s0959-437x(05)80176-5. View

Jones P, Watt F . Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression. Cell. 1993; 73(4):713-24. DOI: 10.1016/0092-8674(93)90251-k. View

Kemler R . From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 1993; 9(9):317-21. DOI: 10.1016/0168-9525(93)90250-l. View

Koch P, Franke W . Desmosomal cadherins: another growing multigene family of adhesion molecules. Curr Opin Cell Biol. 1994; 6(5):682-7. DOI: 10.1016/0955-0674(94)90094-9. View

Shapiro L, Fannon A, Kwong P, Thompson A, Lehmann M, Grubel G . Structural basis of cell-cell adhesion by cadherins. Nature. 1995; 374(6520):327-37. DOI: 10.1038/374327a0. View

10.

Liem Jr K, Tremml G, Roelink H, Jessell T . Dorsal differentiation of neural plate cells induced by BMP-mediated signals from epidermal ectoderm. Cell. 1995; 82(6):969-79. DOI: 10.1016/0092-8674(95)90276-7. View

11.

Dudley A, Lyons K, Robertson E . A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev. 1995; 9(22):2795-807. DOI: 10.1101/gad.9.22.2795. View

12.

Takeichi M . Morphogenetic roles of classic cadherins. Curr Opin Cell Biol. 1995; 7(5):619-27. DOI: 10.1016/0955-0674(95)80102-2. View

13.

Dunne J, Hanby A, Poulsom R, Jones T, Sheer D, Chin W . Molecular cloning and tissue expression of FAT, the human homologue of the Drosophila fat gene that is located on chromosome 4q34-q35 and encodes a putative adhesion molecule. Genomics. 1995; 30(2):207-23. DOI: 10.1006/geno.1995.9884. View

14.

Reynolds B, Weiss S . Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev Biol. 1996; 175(1):1-13. DOI: 10.1006/dbio.1996.0090. View

15.

Pera E, Kessel M . Patterning of the chick forebrain anlage by the prechordal plate. Development. 1997; 124(20):4153-62. DOI: 10.1242/dev.124.20.4153. View

16.

Bradley R, Espeseth A, Kintner C . NF-protocadherin, a novel member of the cadherin superfamily, is required for Xenopus ectodermal differentiation. Curr Biol. 1998; 8(6):325-34. DOI: 10.1016/s0960-9822(98)70132-0. View

17.

Kestila M, Lenkkeri U, Mannikko M, Lamerdin J, McCready P, Putaala H . Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome. Mol Cell. 1998; 1(4):575-82. DOI: 10.1016/s1097-2765(00)80057-x. View

18.

Jacques T, Relvas J, Nishimura S, Pytela R, Edwards G, Streuli C . Neural precursor cell chain migration and division are regulated through different beta1 integrins. Development. 1998; 125(16):3167-77. DOI: 10.1242/dev.125.16.3167. View

19.

Nakayama M, Nakajima D, Nagase T, Nomura N, Seki N, Ohara O . Identification of high-molecular-weight proteins with multiple EGF-like motifs by motif-trap screening. Genomics. 1998; 51(1):27-34. DOI: 10.1006/geno.1998.5341. View

20.

Kim S, Yamamoto A, Bouwmeester T, Agius E, Robertis E . The role of paraxial protocadherin in selective adhesion and cell movements of the mesoderm during Xenopus gastrulation. Development. 1998; 125(23):4681-90. DOI: 10.1242/dev.125.23.4681. View