Transgenic studies on homeobox genes in nervous system development: spina bifida in Isl1 transgenic mice.
To develop in vivo assays for homeobox gene function in neural development, we generated transgenic mice in which the expression of a homeobox gene is altered only within the nervous system, in neurons or neuronal precursor cells. Transgenic expression of Hoxc8 did not result in gross abnormalities, while a Hoxd4 transgene caused death shortly after birth. In neural progenitor cells, the motorneuron-specific homeodomain transcription factor Isl1 induced early developmental defects, including absence of anterior neural structures, profound defects in the neuroepithelium and defective neural tube closure. A fraction of Isl1 transgenic mice exhibited spina bifida. Isl1 transgene expression was also associated with decreased proliferation and increased Pbx1 expression in the ventral neural tube. Our results suggest a function for some homeobox genes in development of the nervous system, and that cell-type- and region-specific transgenic models will be useful to identify the cellular and molecular targets of homeobox transcription factors in nervous system development.
Department of Developmental Biology, Pennington Biomedical Research Center/Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70810, USA. claudia.kappen@pbrc.edu
Claudia
C
Kappen
Paul J
PJ
Yaworsky
Yunhua L
YL
Muller
J Michael
JM
Salbaum
D000818:Animals; D019070:Cell Lineage; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009420:Nervous System / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D054259:Neural Tube / Q000254:growth & development / Q000473:pathology; D016135:Spinal Dysraphism / Q000235:genetics* / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D017405:Herpes Simplex Virus Protein Vmw65; D018398:Homeodomain Proteins; C489816:Hoxc8 protein, mouse; C489520:Hoxd4 protein, mouse; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1