PUBLICATION

Graded levels of Pax2a and Pax8 regulate cell differentiation during sensory placode formation

Authors
McCarroll, M.N., Lewis, Z.R., Culbertson, M.D., Martin, B.L., Kimelman, D., and Nechiporuk, A.V.
ID
ZDB-PUB-120705-40
Date
2012
Source
Development (Cambridge, England)   139(15): 2740-2750 (Journal)
Registered Authors
Culbertson, Maya Deza, Kimelman, David, Lewis, Zachary Robert, Martin, Benjamin, McCarroll, Matthew N., Nechiporuk, Alex
Keywords
none
MeSH Terms
  • Models, Biological
  • Zebrafish
  • Fibroblast Growth Factors/metabolism
  • Time Factors
  • Models, Genetic
  • Animals
  • Crosses, Genetic
  • PAX2 Transcription Factor/metabolism*
  • Ear, Inner/embryology
  • Ear, Inner/physiology
  • Gene Expression Regulation, Developmental*
  • Cell Differentiation
  • Sense Organs
  • Cell Lineage
  • Zebrafish Proteins/metabolism*
  • Paired Box Transcription Factors/metabolism*
(all 16)
PubMed
22745314 Full text @ Development
Abstract

Pax gene haploinsufficiency causes a variety of congenital defects. Renal-coloboma syndrome, resulting from mutations in Pax2, is characterized by kidney hypoplasia, optic nerve malformation, and hearing loss. Although this underscores the importance of Pax gene dosage in normal development, how differential levels of these transcriptional regulators affect cell differentiation and tissue morphogenesis is still poorly understood. We show that differential levels of zebrafish Pax2a and Pax8 modulate commitment and behavior in cells that eventually contribute to the otic vesicle and epibranchial placodes. Initially, a subset of epibranchial placode precursors lie lateral to otic precursors within a single Pax2a/8-positive domain; these cells subsequently move to segregate into distinct placodes. Using lineage-tracing and ablation analyses, we show that cells in the Pax2a/8+ domain become biased towards certain fates at the beginning of somitogenesis. Experiments involving either Pax2a overexpression or partial, combinatorial Pax2a and Pax8 loss of function reveal that high levels of Pax favor otic differentiation whereas low levels increase cell numbers in epibranchial ganglia. In addition, the Fgf and Wnt signaling pathways control Pax2a expression: Fgf is necessary to induce Pax2a, whereas Wnt instructs the high levels of Pax2a that favor otic differentiation. Our studies reveal the importance of Pax levels during sensory placode formation and provide a mechanism by which these levels are controlled.

Genes / Markers
Figures
Figure Gallery (19 images) / 2
Show all Figures
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b593
    Unknown
    e1TgTransgenic Insertion
      pd1TgTransgenic Insertion
        pd3TgTransgenic Insertion
          w32TgTransgenic Insertion
            w37TgTransgenic Insertion
              w74TgTransgenic Insertion
                1 - 7 of 7
                Show
                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                Target Reagent Reagent Type
                pax2aMO4-pax2aMRPHLNO
                pax8MO4-pax8MRPHLNO
                pax8MO5-pax8MRPHLNO
                1 - 3 of 3
                Show
                Fish
                Antibodies
                Orthology
                No data available
                Engineered Foreign Genes
                Marker Marker Type Name
                DsRedEFGDsRed
                EGFPEFGEGFP
                GFPEFGGFP
                1 - 3 of 3
                Show
                Mapping
                No data available