Hedgehog-dependent down-regulation of the tumor suppressor, vitamin D3 up-regulated protein 1 (VDUP1), precedes lamina development in Drosophila.
The tumor suppressor vitamin D(3) up-regulated protein 1 (VDUP1) is expressed throughout the developing and mature Drosophila nervous system, but its regulatory pathways are not well understood. Within the developing Drosophila visual system, down-regulation of VDUP1 in lamina precursor cells (LPCs) coincided with the arrival of retinal axons into the lamina target field, suggesting VDUP1 regulation by an axonally transmitted signal. Hedgehog (Hh) is a signal well known to coordinate LPC proliferation and differentiation in response to retinal axon innervation, and analysis of orthologous dvdup1 promoters identified an evolutionarily conserved binding site for the Hh-dependent transcription factor cubitus interruptus (Ci). Hh-dependent regulation of VDUP1 in the developing lamina was confirmed in Hh loss-of-function backgrounds where VDUP1 expression was maintained in LPCs, inhibiting both cell proliferation and lamina neurogenesis. This putative coupling of VDUP1 to the Hh signaling pathway may provide novel insights into the mechanisms controlling brain growth and development.
Chang
Solomon
S
Albany College of Pharmacy and Health Sciences, Department of Pharmaceutical Sciences, 9 Samaritan Road, Albany, NY 12208, USA.
Mandalaywala
Neil V
NV
Snyder
Randall G
RG
Levendusky
Mark C
MC
Dearborn
Richard E
RE
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D054910:Compound Eye, Arthropod / Q000254:growth & development / Q000502:physiology; D017124:Conserved Sequence; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D008959:Models, Neurological; D008969:Molecular Sequence Data; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000502:physiology; D009899:Optic Lobe, Nonmammalian / Q000254:growth & development / Q000502:physiology; D055351:Retinal Neurons / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D014795:Visual Pathways / Q000254:growth & development / Q000502:physiology
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; C547180:VDUP1 protein, Drosophila; C077245:hh protein, Drosophila