title: Dorsoventral patterning of the Xenopus eye involves differential temporal changes in the response of optic stalk and retinal progenitors to Hh signalling.
abstract: BACKGROUND
  Hedgehog (Hh) signals are instrumental to the dorsoventral patterning of the vertebrate eye, promoting optic stalk and ventral retinal fates and repressing dorsal retinal identity. There has been limited analysis, however, of the critical window during which Hh molecules control eye polarity and of the temporal changes in the responsiveness of eye cells to these signals.
  
  
  RESULTS
  In this study, we used pharmacological and molecular tools to perform stage-specific manipulations of Hh signalling in the developing Xenopus eye. In gain-of-function experiments, most of the eye was sensitive to ventralization when the Hh pathway was activated starting from gastrula/neurula stages. During optic vesicle stages, the dorsal eye became resistant to Hh-dependent ventralization, but this pathway could partially upregulate optic stalk markers within the retina. In loss-of-function assays, inhibition of Hh signalling starting from neurula stages caused expansion of the dorsal retina at the expense of the ventral retina and the optic stalk, while the effects of Hh inhibition during optic vesicle stages were limited to the reduction of optic stalk size.
  
  
  CONCLUSIONS
  Our results suggest the existence of two competence windows during which the Hh pathway differentially controls patterning of the eye region. In the first window, between the neural plate and the optic vesicle stages, Hh signalling exerts a global influence on eye dorsoventral polarity, contributing to the specification of optic stalk, ventral retina and dorsal retinal domains. In the second window, between optic vesicle and optic cup stages, this pathway plays a more limited role in the maintenance of the optic stalk domain. We speculate that this temporal regulation is important to coordinate dorsoventral patterning with morphogenesis and differentiation processes during eye development.
authors.affiliation: The State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101, China. 13522764597@163.com.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK. giuseppe.lupo@uniroma1.it.|Department of Chemistry, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy. giuseppe.lupo@uniroma1.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lupo
authors.affiliation: The State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101, China. herq@ibp.ac.cn.
authors.forename: Rongqiao
authors.initials: R
authors.lastname: He
authors.affiliation: Dipartimento di Biologia, Unità di Biologia Cellulare e dello Sviluppo, Università di Pisa, SS 12 Abetone e Brennero 4, 56127, Pisa, Italy. gbarsacchi41@gmail.com.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Barsacchi
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK. wah20@cam.ac.uk.
authors.forename: William A
authors.initials: WA
authors.lastname: Harris
authors.affiliation: The State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101, China. liuy@moon.ibp.ac.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000502:physiology; D005123:Eye / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D053823:Hedgehog Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D009025:Morpholines / Q000494:pharmacology; D054258:Neural Plate / Q000196:embryology; D009479:Neuropeptides / Q000096:biosynthesis / Q000235:genetics; D054261:Neurulation / Q000187:drug effects; D051762:PAX2 Transcription Factor / Q000096:biosynthesis / Q000235:genetics; D011687:Purines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012160:Retina / Q000196:embryology; D015398:Signal Transduction / Q000187:drug effects; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors; D029867:Xenopus Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014982:Xenopus laevis / Q000196:embryology
chemical_list: D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D009025:Morpholines; D009479:Neuropeptides; D051762:PAX2 Transcription Factor; D011687:Purines; D011994:Recombinant Proteins; C465570:Shh protein, mouse; D020825:T-Box Domain Proteins; C491459:Tbx3 protein, Xenopus; C113864:Vax1 protein, Xenopus; D029867:Xenopus Proteins; C492361:vax2 protein, Xenopus; C470893:purmorphamine