1. Academic Validation
  2. Deficiency of the cytoskeletal protein SPECC1L leads to oblique facial clefting

Deficiency of the cytoskeletal protein SPECC1L leads to oblique facial clefting

  • Am J Hum Genet. 2011 Jul 15;89(1):44-55. doi: 10.1016/j.ajhg.2011.05.023.
Irfan Saadi 1 Fowzan S Alkuraya Stephen S Gisselbrecht Wolfram Goessling Resy Cavallesco Annick Turbe-Doan Aline L Petrin James Harris Ursela Siddiqui Arthur W Grix Jr Hanne D Hove Philippe Leboulch Thomas W Glover Cynthia C Morton Antonio Richieri-Costa Jeffrey C Murray Robert P Erickson Richard L Maas
Affiliations

Affiliation

  • 1 Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. [email protected]
Abstract

Genetic mutations responsible for oblique facial clefts (ObFC), a unique class of facial malformations, are largely unknown. We show that loss-of-function mutations in SPECC1L are pathogenic for this human developmental disorder and that SPECC1L is a critical organizer of vertebrate facial morphogenesis. During murine embryogenesis, Specc1l is expressed in cell populations of the developing facial primordial, which proliferate and fuse to form the face. In zebrafish, knockdown of a SPECC1L homolog produces a faceless phenotype with loss of jaw and facial structures, and knockdown in Drosophila phenocopies mutants in the Integrin signaling pathway that exhibit cell-migration and -adhesion defects. Furthermore, in mammalian cells, SPECC1L colocalizes with both tubulin and actin, and its deficiency results in defective actin-cytoskeleton reorganization, as well as abnormal cell adhesion and migration. Collectively, these data demonstrate that SPECC1L functions in actin-cytoskeleton reorganization and is required for proper facial morphogenesis.

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