1. Elsen GE, Choi LY, Prince VE, Ho RK. {{The autism susceptibility gene met regulates zebrafish cerebellar development and facial motor neuron migration}}. {Dev Biol};2009 (Sep 1)
During development, Met signaling regulates a range of cellular processes including growth, differentiation, survival and migration. The Met gene encodes a tyrosine kinase receptor, which is activated by Hgf (hepatocyte growth factor) ligand. Altered regulation of human MET expression has been implicated in autism. In mouse, Met signaling has been shown to regulate cerebellum development. Since abnormalities in cerebellar structure have been reported in some autistic patients, we have used the zebrafish to address the role of Met signaling during cerebellar development and thus further our understanding of the molecular basis of autism. We find that zebrafish met is expressed in the cerebellar primordium, later localizing to the ventricular zone (VZ), with the hgf1 and hgf2 ligand genes expressed in surrounding tissues. Morpholino knockdown of either Met or its Hgf ligands leads to a significant reduction in the size of the cerebellum, primarily as a consequence of reduced proliferation. Met signaling knockdown disrupts specification of VZ-derived cell types, and also reduces granule cell numbers, due to an early effect on cerebellar proliferation and/or as an indirect consequence of loss of signals from VZ-derived cells later in development. These patterning defects preclude analysis of cerebellar neuronal migration, but we have found that Met signaling is necessary for migration of hindbrain facial motor neurons. In summary, we have described roles for Met signaling in coordinating growth and cell type specification within the developing cerebellum, and in migration of hindbrain neurons. These functions may underlie the correlation between altered MET regulation and Autism Spectrum Disorders.
2. Geschwind D. {{The vaccine-autism controversy}}. {Nat Med};2009 (Sep);15(9):992.
3. Robel L. {{[Clinical features in autism.]}}. Arch Pediatr;2009 (Sep 2){{Donnees actuelles sur la clinique de l’autisme}}.
Autism is a neurodevelopmental disorder diagnosed on the basis of three behaviorally altered domains: social deficits, impaired language and communication, and stereotyped and repetitive behaviors. The early recognition of the disorder, as early as 2 years, is an important challenge, because early treatments are more efficient in helping children to develop their adaptation skills, allowing their better integration in the society, with less suffering and a lower level of handicap. Therefore, we describe the symptoms that may lead first degree practioners to suspect autistic disorders as early as possible, and how they can help the children and their parents to be directed to the appropriate services for diagnostic and treatment.
