Specification of the anterior hindbrain and establishment of a normal mid/hindbrain organizer is dependent on Gbx2 gene function.
Analysis of mouse embryos homozygous for a loss-of-function allele of Gbx2 demonstrates that this homeobox gene is required for normal development of the mid/hindbrain region. Gbx2 function appears to be necessary at the neural plate stage for the correct specification and normal proliferation or survival of anterior hindbrain precursors. It is also required to maintain normal patterns of expression at the mid/hindbrain boundary of Fgf8 and Wnt1, genes that encode signaling molecules thought to be key components of the mid/hindbrain (isthmic) organizer. In the absence of Gbx2 function, isthmic nuclei, the cerebellum, motor nerve V, and other derivatives of rhombomeres 1-3 fail to form. Additionally, the posterior midbrain in the mutant embryos appears to be extended caudally and displays abnormalities in anterior/posterior patterning. The failure of anterior hindbrain development is presumably due to the loss of Gbx2 function in the precursors of the anterior hindbrain. However, since Gbx2 expression is not detected in the midbrain it seems likely that the defects in midbrain anterior/posterior patterning result from an abnormal isthmic signaling center. These data provide genetic evidence for a link between patterning of the anterior hindbrain and the establishment of the mid/hindbrain organizer, and identify Gbx2 as a gene required for these processes to occur normally.
Wassarman
K M
KM
Department of Anatomy and Program in Developmental Biology, School of Medicine, University of California, San Francisco 94143-0452, USA.
Lewandoski
M
M
Campbell
K
K
Joyner
A L
AL
Rubenstein
J L
JL
Martinez
S
S
Martin
G R
GR
D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002531:Cerebellum / Q000196:embryology; D036383:Ephrin-A2; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D005775:Gastrula; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox / Q000502:physiology*; D006133:Growth Substances / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D006720:Homozygote; D008636:Mesencephalon / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics; D051857:Otx Transcription Factors; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012249:Rhombencephalon / Q000196:embryology*; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D036383:Ephrin-A2; C496457:Fgf8 protein, mouse; C513182:Gbx2 protein, mouse; D006133:Growth Substances; C101121:HOXB1 homeodomain protein; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins; C513181:gbx2 protein, zebrafish; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors