BMP7 and SHH regulate Pax2 in mouse retinal astrocytes by relieving TLX repression.
Pax2 is essential for development of the neural tube, urogenital system, optic vesicle, optic cup and optic tract. In the eye, Pax2 deficiency is associated with coloboma, a loss of astrocytes in the optic nerve and retina, and abnormal axonal pathfinding of the ganglion cell axons at the optic chiasm. Thus, appropriate expression of Pax2 is essential for astrocyte determination and differentiation. Although BMP7 and SHH have been shown to regulate Pax2 expression, the molecular mechanism by which this regulation occurs is not well understood. In this study, we determined that BMP7 and SHH activate Pax2 expression in mouse retinal astrocyte precursors in vitro. SHH appeared to play a dual role in Pax2 regulation; 1) SHH may regulate BMP7 expression, and 2) the SHH pathway cooperates with the BMP pathway to regulate Pax2 expression. BMP and SHH pathway members can interact separately or together with TLX, a repressor protein in the tailless transcription factor family. Here we show that the interaction of both pathways with TLX relieves the repression of Pax2 expression in mouse retinal astrocytes. Together these data reveal a new mechanism for the cooperative actions of signaling pathways in astrocyte determination and differentiation and suggest interactions of regulatory pathways that are applicable to other developmental programs.
Sehgal
Rachna
R
Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN-46202, USA.
Sheibani
Nader
N
Rhodes
Simon J
SJ
Belecky Adams
Teri L
TL
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism*; D038681:Follistatin / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D014704:Veratrum Alkaloids / Q000378:metabolism; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
D055419:Bone Morphogenetic Protein 7; D038681:Follistatin; C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; C490258:Nr2e1 protein, mouse; D051762:PAX2 Transcription Factor; D018160:Receptors, Cytoplasmic and Nuclear; C465570:Shh protein, mouse; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D014704:Veratrum Alkaloids; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; C000541:cyclopamine