SPECIFICATION OF THE ANTERIOR HINDBRAIN AND ESTABLISHMENT OF A NORMALMID 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 required for normal development o f the mid/hindbrain region. Gbx2 function appears to be necessary at t he neural plate stage for the correct specification and normal prolife ration or survival of anterior hindbrain precursors, It is also requir ed to maintain normal patterns of expression at the mid/hindbrain boun dary of Fgf8 and Wnt1, genes that encode signaling molecules thought t o be key components of the mid/hindbrain (isthmic) organizer, In the a bsence 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 c audally and displays abnormalities in anterior/posterior patterning, T he failure of anterior hindbrain development is presumably due to the loss of Gbx2 function in the precursors of the anterior hindbrain, How ever, since Gbx2 expression is not detected in the midbrain it seems l ikely that the defects in midbrain anterior/posterior patterning resul t from an abnormal isthmic signaling center. These data provide geneti c evidence for a link between patterning of the anterior hindbrain and the establishment of the mid/hindbrain organizer, and identify Gbx2 a s a gene required for these processes to occur normally.