Defects in brain patterning and head morphogenesis in the mouse mutant Fused toes.
During vertebrate development, brain patterning and head morphogenesis are tightly coordinated. In this paper, we study these processes in the mouse mutant Fused toes (Ft), which presents severe head defects at midgestation. The Ft line carries a 1.6-Mb deletion on chromosome 8. This deletion eliminates six genes, three members of the Iroquois gene family, Irx3, Irx5 and Irx6, which form the IrxB cluster, and three other genes of unknown function, Fts, Ftm and Fto. We show that in Ft/Ft embryos, both anteroposterior and dorsoventral patterning of the brain are affected. As soon as the beginning of somitogenesis, the forebrain is expanded caudally and the midbrain is reduced. Within the expanded forebrain, the most dorsomedial (medial pallium) and ventral (hypothalamus) regions are severely reduced or absent. Morphogenesis of the forebrain and optic vesicles is strongly perturbed, leading to reduction of the eyes and delayed or absence of neural tube closure. Finally, facial structures are hypoplastic. Given the diversity, localisation and nature of the defects, we propose that some of them are caused by the elimination of the IrxB cluster, while others result from the loss of one or several of the Fts, Ftm and Fto genes.
Anselme
Isabelle
I
Biologie du Développement, CNRS UMR7622, Université Pierre et Marie Curie, 9 Quai Saint-Bernard, 75252 Paris Cedex 05, France.
Laclef
Christine
C
Lanaud
Magali
M
Rüther
Ulrich
U
Schneider-Maunoury
Sylvie
S
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D019521:Body Patterning / Q000235:genetics / Q000502:physiology*; D001921:Brain / Q000196:embryology*; D002872:Chromosome Deletion; D006257:Head / Q000196:embryology*; D018398:Homeodomain Proteins / Q000235:genetics; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; C109729:Fts protein, mouse; D018398:Homeodomain Proteins; C501599:Irx3 protein, mouse; C501601:Irx5 protein, mouse; C501605:Irx6 protein, mouse; D011506:Proteins; D014157:Transcription Factors