Wnt signaling is required at distinct stages of development for the induction of the posterior forebrain.
One of the earliest manifestations of anteroposterior pattering in the developing brain is the restricted expression of Six3 and Irx3 in the anterior and posterior forebrain, respectively. Consistent with the role of Wnts as posteriorizing agents in neural tissue, we found that Wnt signaling was sufficient to induce Irx3 and repress Six3 expression in forebrain explants. The position of the zona limitans intrathalamica (zli), a boundary-cell population that develops between the ventral (vT) and dorsal thalamus (dT), is predicted by the apposition of Six3 and Irx3 expression domains. The expression patterns of several inductive molecules are limited by the zli, including Wnt3, which is expressed posterior to the zli in the dT. Wnt3 and Wnt3a were sufficient to induce the dT marker Gbx2 exclusively in explants isolated posterior to the presumptive zli. Blocking the Wnt response allowed the induction of the vT-specific marker Dlx2 in prospective dT tissue. Misexpression of Six3 in the dT induced Dlx2 expression and inhibited the expression of both Gbx2 and Wnt3. These results demonstrate a dual role for Wnt signaling in forebrain development. First, Wnts directed the initial expression of Irx3 and repression of Six3 in the forebrain, delineating posterior and anterior forebrain domains. Later, continued Wnt signaling resulted in the induction of dT specific markers, but only in tissues that expressed Irx3.
Braun
Michelle M
MM
Program in Neurobiology and Behavior, Department of Biological Structure, Box 357420, University of Washington, Seattle, WA 98195, USA.
Etheridge
Alton
A
Bernard
Amy
A
Robertson
Christie P
CP
Roelink
Henk
H
D000818:Animals; D019521:Body Patterning; D002454:Cell Differentiation / Q000502:physiology; D002642:Chick Embryo / Q000033:anatomy & histology / Q000502:physiology*; D046508:Culture Techniques; D005136:Eye Proteins; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017403:In Situ Hybridization; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000097607:Homeobox Protein SIX3
D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D000097607:Homeobox Protein SIX3; C501593:irx1a protein, zebrafish