Jak-STAT Gradient Drives Rearrangement

Abstract

During organogenesis many processes occur, including cell growth, cell division, cell death, and cell rearrangement. Johansen et al. investigated Drosophila hindgut cell rearrangement (cells go from forming a wide, short tubular structure with many cells in the circumference to forming a narrow, elongated tubular structure with fewer cells in the circumference) during hindgut organogenesis. Wingless (wg), which is involved in many morphogenesis and patterning processes, is not required during the period of hindgut elongation; although wg is necessary before elongation. Unpaired (upd), which encodes the ligand for the Drosophila Janus kinase-signal transducer and activator of transcription (Jak-STAT) signaling cascade, is expressed in the small intestine of the anterior hindgut during elongation, as are the receptor (dome) and STAT92E, which are expressed more broadly. Using combinations of gain-of-function and loss-of-function mutants for the Jak-STAT pathway, the authors showed that upd expression had to be restricted to the anterior small intestine for proper hindgut elongation. Expression of STAT92E was stimulated in cells from the small intestine and large intestine and increased STAT92E was detected when upd was uniformly expressed, confirming that upd stimulated Stat92E expression. To confirm that upd must be released and must act as a signal (not cell autonomously), an activated Jak (hopTML) was expressed in the anterior hindgut of upd mutants and did not rescue the upd phenotype. Thus, the Jak-STAT pathway appears to be activated in a graded fashion to promote proper development.K. A. Johansen, D. D. Iwaki, J. A. Lengyel, Localized JAK/STAT signaling is required for oriented cell rearrangement in a tubular epithelium. Development 130, 135-145 (2002). [Abstract] [Full Text]