Rx3 and Shh direct anisotropic growth and specification in the zebrafish tuberal/anterior hypothalamus.
In the developing brain, growth and differentiation are intimately linked. Here, we show that in the zebrafish embryo, the homeodomain transcription factor Rx3 coordinates these processes to build the tuberal/anterior hypothalamus. Analysis of rx3 chk mutant/rx3 morphant fish and EdU pulse-chase studies reveal that rx3 is required to select tuberal/anterior hypothalamic progenitors and to orchestrate their anisotropic growth. In the absence of Rx3 function, progenitors accumulate in the third ventricular wall, die or are inappropriately specified, the shh(+) anterior recess does not form, and its resident pomc(+), ff1b(+) and otpb(+) Th1(+) cells fail to differentiate. Manipulation of Shh signalling shows that Shh coordinates progenitor cell selection and behaviour by acting as an on-off switch for rx3 Together, our studies show that Shh and Rx3 govern formation of a distinct progenitor domain that elaborates patterning through its anisotropic growth and differentiation.
The Bateson Centre and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Victor
V
Muthu
The Bateson Centre and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
Helen
H
Eachus
The Bateson Centre and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
Pam
P
Ellis
The Bateson Centre and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.
Sarah
S
Brown
The Bateson Centre and Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK m.placzek@sheffield.ac.uk.
Marysia
0000-0002-4106-9229
M
Placzek
D000818:Animals; D016880:Anisotropy; D019521:Body Patterning; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D053823:Hedgehog Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D007032:Hypothalamus, Anterior / Q000254:growth & development* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015027:Zebrafish / Q000254:growth & development* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; C488383:Rx3 protein, zebrafish; C524053:Shha protein, zebrafish; D029961:Zebrafish Proteins
Anterior hypothalamus; Hypothalamus development; Rx3; Sonic hedgehog; Tuberal hypothalamus; Zebrafish hypothalamus